Stromal Modulators of TGF-β in Cancer

[en] Transforming growth factor-β (TGF-β) is an intriguing cytokine exhibiting dual activities in malignant disease. It is an important mediator of cancer invasion, metastasis and angiogenesis, on the one hand, while it exhibits anti-tumor functions on the other hand. Elucidating the precise role of TGF-β in malignant development and progression requires a better understanding of the molecular mechanisms involved in its tumor suppressor to tumor promoter switch. One important aspect of TGF-β function is its interaction with proteins within the tumor microenvironment. Several stromal proteins have the natural ability to interact and modulate TGF-β function. Understanding the complex interplay between the TGF-β signaling network and these stromal proteins may provide greater insight into the development of novel therapeutic strategies that target the TGF-β axis. The present review highlights our present understanding of how stroma modulates TGF-β activity in human cancers

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Costanza, Brunella ; Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (paysage)

Umelo, Ijeoma ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Bellier, Justine ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Turtoi, Andrei ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Castronovo, Vincenzo ; Université de Liège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire

Language :

English

Title :

Stromal Modulators of TGF-β in Cancer

Publication date :

06 January 2017

Journal title :

Journal of Clinical Medicine

eISSN :

2077-0383

Publisher :

MDPI, Basel, Switzerland

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 19 February 2017

Statistics

Number of views

141 (18 by ULiège)

Number of downloads

202 (16 by ULiège)

More statistics

Scopus citations^®

128

Scopus citations^®
without self-citations

125

OpenCitations

109

Bibliography

Imamura, T., Hikita, A., Inoue, Y. The roles of TGF-β signaling in carcinogenesis and breast cancer metastasis. Breast Cancer 2012, 19, 118-124.
Bierie, B., Moses, H.L. Tumour microenvironment: TGFβ: The molecular jekyll and hyde of cancer. Nat. Rev. Cancer 2006, 6, 506-520.
Akhurst, R.J., Derynck, R. TGF-β signaling in cancer—A double-edged sword. Trends Cell Biol. 2001, 11, S44-S51.
Derynck, R., Zhang, Y.E. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature 2003, 425, 577-584.
Massague, J., Blain, S.W., Lo, R.S. TGFβ signaling in growth control, cancer, and heritable disorders. Cell 2000, 103, 295-309.
Shi, Y., Massague, J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 2003, 113, 685-700.
Zhang, Y.E. Non-Smad pathways in TGF-β signaling. Cell Res. 2009, 19, 128-139.
Padua, D., Massague, J. Roles of TGFβ in metastasis. Cell Res. 2009, 19, 89-102.
Neuzillet, C., Tijeras-Raballand, A., Cohen, R., Cros, J., Faivre, S., Raymond, E., de Gramont, A. Targeting the TGFβ pathway for cancer therapy. Pharmacol. Ther. 2015, 147, 22-31.
Huse, M., Muir, T.W., Xu, L., Chen, Y.G., Kuriyan, J., Massague, J. The TGFβ receptor activation process: An inhibitor-to substrate-binding switch. Mol. Cell 2001, 8, 671-682.
Kretzschmar, M., Massague, J. Smads: Mediators and regulators of TGF-β signaling. Curr. Opin. Genet. Dev. 1998, 8, 103-111.
Levy, L., Hill, C.S. Alterations in components of the TGF-β superfamily signaling pathways in human cancer. Cytokine Growth Factor Rev. 2006, 17, 41-58.
Bierie, B., Moses, H.L. TGF-β and cancer. Cytokine Growth Factor Rev. 2006, 17, 29-40.
Muller-Pillasch, F., Menke, A., Yamaguchi, H., Elsasser, H.P., Bachem, M., Adler, G., Gress, T.M. TGFβ and the extracellular matrix in pancreatitis. Hepatogastroenterology 1999, 46, 2751-2756.
Ikushima, H., Miyazono, K. TGFβ signalling: A complex web in cancer progression. Nat. Rev. Cancer 2010, 10, 415-424.
Meulmeester, E., Ten Dijke, P. The dynamic roles of TGF-β in cancer. J. Pathol. 2011, 223, 205-218.
Tang, B., Vu, M., Booker, T., Santner, S.J., Miller, F.R., Anver, M.R., Wakefield, L.M. TGF-β switches from tumor suppressor to prometastatic factor in a model of breast cancer progression. J. Clin. Investig. 2003, 112, 1116-1124.
Jang, C.W., Chen, C.H., Chen, C.C., Chen, J.Y., Su, Y.H., Chen, R.H. TGF-β induces apoptosis through Smad-mediated expression of dap-kinase. Nat. Cell Biol. 2002, 4, 51-58.
Perlman, R., Schiemann, W.P., Brooks, M.W., Lodish, H.F., Weinberg, R.A. TGF-β-induced apoptosis is mediated by the adapter protein daxx that facilitates jnk activation. Nat. Cell Biol. 2001, 3, 708-714.
Yoo, J., Ghiassi, M., Jirmanova, L., Balliet, A.G., Hoffman, B., Fornace, A.J., Jr., Liebermann, D.A., Bottinger, E.P., Roberts, A.B. Transforming growth factor-β-induced apoptosis is mediated by Smaddependent expression of GADD45b through p38 activation. J. Biol. Chem. 2003, 278, 43001-43007.
Pickup, M., Novitskiy, S., Moses, H.L. The roles of TGFβ in the tumour microenvironment. Nat. Rev. Cancer 2013, 13, 788-799.
Agajanian, M., Campeau, A., Hoover, M., Hou, A., Brambilla, D., Kim, S.L., Klemke, R.L., Kelber, J.A. Peak1 acts as a molecular switch to regulate context-dependent TGFβ responses in breast cancer. PLoS ONE 2015, 10, e0135748.
Wilson, T.J., Singh, R.K. Proteases as modulators of tumor-stromal interaction: Primary tumors to bone metastases. Biochim. Biophys. Acta 2008, 1785, 85-95.
Massague, J. TGF-β signaling in development and disease. FEBS Lett. 2012, 586, 1833.
Prakash, J. Cancer-associated fibroblasts: Perspectives in cancer therapy. Trends Cancer 2016, 2, 277-279.
Calon, A., Espinet, E., Palomo-Ponce, S., Tauriello, D.V., Iglesias, M., Cespedes, M.V., Sevillano, M., Nadal, C., Jung, P., Zhang, X.H., et al. Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell 2012, 22, 571-584.
Calon, A., Lonardo, E., Berenguer-Llergo, A., Espinet, E., Hernando-Momblona, X., Iglesias, M., Sevillano, M., Palomo-Ponce, S., Tauriello, D.V., Byrom, D., et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat. Genet. 2015, 47, 320-329.
Annes, J.P., Munger, J.S., Rifkin, D.B. Making sense of latent TGF-β activation. J. Cell Sci. 2003, 116, 217-224.
Horiguchi, M., Ota, M., Rifkin, D.B. Matrix control of transforming growth factor-β function. J. Biochem. 2012, 152, 321-329.
Ten Dijke, P., Arthur, H.M. Extracellular control of TGFβ signalling in vascular development and disease. Nat. Rev. Mol. Cell Biol. 2007, 8, 857-869.
Richardsen, E., Uglehus, R.D., Johnsen, S.H., Busund, L.T. Immunohistochemical expression of epithelial and stromal immunomodulatory signalling molecules is a prognostic indicator in breast cancer. BMC Res. Notes 2012, 5, 110.
Tsushima, H., Kawata, S., Tamura, S., Ito, N., Shirai, Y., Kiso, S., Imai, Y., Shimomukai, H., Nomura, Y., Matsuda, Y., et al. High levels of transforming growth factor β1 in patients with colorectal cancer: Association with disease progression. Gastroenterology 1996, 110, 375-382.
Steiner, M.S., Barrack, E.R. Transforming growth factor-β1 overproduction in prostate cancer: Effects on growth in vivo and in vitro. Mol. Endocrinol. 1992, 6, 15-25.
Bhowmick, N.A., Chytil, A., Plieth, D., Gorska, A.E., Dumont, N., Shappell, S., Washington, M.K., Neilson, E.G., Moses, H.L. TGF-β signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 2004, 303, 848-851.
Li, X., Sterling, J.A., Fan, K.H., Vessella, R.L., Shyr, Y., Hayward, S.W., Matrisian, L.M., Bhowmick, N.A. Loss of TGF-β responsiveness in prostate stromal cells alters chemokine levels and facilitates the development of mixed osteoblastic/osteolytic bone lesions. Mol. Cancer Res. 2012, 10, 494-503.
Bierie, B., Moses, H.L. Transforming growth factor β (TGF-β) and inflammation in cancer. Cytokine Growth Factor Rev. 2010, 21, 49-59.
Guido, C., Whitaker-Menezes, D., Capparelli, C., Balliet, R., Lin, Z., Pestell, R.G., Howell, A., Aquila, S., Ando, S., Martinez-Outschoorn, U., et al. Metabolic reprogramming of cancer-associated fibroblasts by TGF-β drives tumor growth: Connecting TGF-β signaling with “warburg-like” cancer metabolism and l-lactate production. Cell Cycle 2012, 11, 3019-3035.
Elenbaas, B., Weinberg, R.A. Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation. Exp. Cell Res. 2001, 264, 169-184.
Novitskiy, S.V., Forrester, E., Pickup, M.W., Gorska, A.E., Chytil, A., Aakre, M., Polosukhina, D., Owens, P., Yusupova, D.R., Zhao, Z., et al. Attenuated transforming growth factor β signaling promotes metastasis in a model of her2 mammary carcinogenesis. Breast Cancer Res. 2014, 16, 425.
Cho, H.J., Baek, K.E., Saika, S., Jeong, M.J., Yoo, J. Snail is required for transforming growth factor-β-induced epithelial-mesenchymal transition by activating pi3 kinase/akt signal pathway. Biochem. Biophys. Res. Commun. 2007, 353, 337-343.
Naber, H.P., Drabsch, Y., Snaar-Jagalska, B.E., ten Dijke, P., van Laar, T. Snail and slug, key regulators of TGF-β-induced emt, are sufficient for the induction of single-cell invasion. Biochem. Biophys. Res. Commun. 2013, 435, 58-63.
Franci, C., Gallen, M., Alameda, F., Baro, T., Iglesias, M., Virtanen, I., Garcia de Herreros, A. Snail1 protein in the stroma as a new putative prognosis marker for colon tumours. PLoS ONE 2009, 4, e5595.
Ji, Q., Liu, X., Han, Z., Zhou, L., Sui, H., Yan, L., Jiang, H., Ren, J., Cai, J., Li, Q. Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated snail/e-cadherin expression. BMC Cancer 2015, 15, 97.
Dhasarathy, A., Phadke, D., Mav, D., Shah, R.R., Wade, P.A. The transcription factors snail and slug activate the transforming growth factor-β signaling pathway in breast cancer. PLoS ONE 2011, 6, e26514.
Liu, R.Y., Zeng, Y., Lei, Z., Wang, L., Yang, H., Liu, Z., Zhao, J., Zhang, H.T. Jak/stat3 signaling is required for TGF-β-induced epithelial-mesenchymal transition in lung cancer cells. Int. J. Oncol. 2014, 44, 1643-1651.
Kokudo, T., Suzuki, Y., Yoshimatsu, Y., Yamazaki, T., Watabe, T., Miyazono, K. Snail is required for TGFβ-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. J. Cell Sci. 2008, 121, 3317-3324.
Matise, L.A., Palmer, T.D., Ashby, W.J., Nashabi, A., Chytil, A., Aakre, M., Pickup, M.W., Gorska, A.E., Zijlstra, A., Moses, H.L. Lack of transforming growth factor-β signaling promotes collective cancer cell invasion through tumor-stromal crosstalk. Breast Cancer Res. 2012, 14, R98.
Orlova, V.V., Liu, Z., Goumans, M.J., ten Dijke, P. Controlling angiogenesis by two unique TGF-β type I receptor signaling pathways. Histol. Histopathol. 2011, 26, 1219-1230.
Bertolino, P., Deckers, M., Lebrin, F., ten Dijke, P. Transforming growth factor-β signal transduction in angiogenesis and vascular disorders. Chest 2005, 128, 585S-590S.
Yang, F., Strand, D.W., Rowley, D.R. Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma. Oncogene 2008, 27, 450-459.
Donovan, D., Harmey, J.H., Toomey, D., Osborne, D.H., Redmond, H.P., Bouchier-Hayes, D.J. TGF-β-1 regulation of vegf production by breast cancer cells. Ann. Surg. Oncol. 1997, 4, 621-627.
Nakagawa, T., Lan, H.Y., Zhu, H.J., Kang, D.H., Schreiner, G.F., Johnson, R.J. Differential regulation of vegf by TGF-β and hypoxia in rat proximal tubular cells. Am. J. Physiol. Renal. Physiol. 2004, 287, F658-F664.
Igarashi, A., Okochi, H., Bradham, D.M., Grotendorst, G.R. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair. Mol. Biol. Cell 1993, 4, 637-645.
Fischer, A.N., Fuchs, E., Mikula, M., Huber, H., Beug, H., Mikulits, W. Pdgf essentially links TGF-β signaling to nuclear β-catenin accumulation in hepatocellular carcinoma progression. Oncogene 2007, 26, 3395-3405.
Ferrari, G., Cook, B.D., Terushkin, V., Pintucci, G., Mignatti, P. Transforming growth factor-β1 (TGF-β1) induces angiogenesis through vascular endothelial growth factor (VEGF)-mediated apoptosis. J. Cell Physiol. 2009, 219, 449-458.
Geng, L., Chaudhuri, A., Talmon, G., Wisecarver, J.L., Wang, J. TGF-β suppresses VEGFA-mediated angiogenesis in colon cancer metastasis. PLoS ONE 2013, 8, e59918.
Nakagawa, T., Li, J.H., Garcia, G., Mu, W., Piek, E., Bottinger, E.P., Chen, Y., Zhu, H.J., Kang, D.H., Schreiner, G.F., et al. TGF-β induces proangiogenic and antiangiogenic factors via parallel but distinct Smad pathways. Kidney Int. 2004, 66, 605-613.
Goumans, M.J., Valdimarsdottir, G., Itoh, S., Rosendahl, A., Sideras, P., ten Dijke, P. Balancing the activation state of the endothelium via two distinct TGF-β type i receptors. EMBO J. 2002, 21, 1743-1753.
Sutton, A.B., Canfield, A.E., Schor, S.L., Grant, M.E., Schor, A.M. The response of endothelial cells to TGF β-1 is dependent upon cell shape, proliferative state and the nature of the substratum. J. Cell Sci. 1991, 99, 777-787.
Pavlides, S., Tsirigos, A., Migneco, G., Whitaker-Menezes, D., Chiavarina, B., Flomenberg, N., Frank, P.G., Casimiro, M.C., Wang, C., Pestell, R.G., et al. The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle 2010, 9, 3485-3505.
Martinez-Outschoorn, U.E., Trimmer, C., Lin, Z., Whitaker-Menezes, D., Chiavarina, B., Zhou, J., Wang, C., Pavlides, S., Martinez-Cantarin, M.P., Capozza, F., et al. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFkappaB activation in the tumor stromal microenvironment. Cell Cycle 2010, 9, 3515-3533.
Sotgia, F., Martinez-Outschoorn, U.E., Howell, A., Pestell, R.G., Pavlides, S., Lisanti, M.P. Caveolin-1 and cancer metabolism in the tumor microenvironment: Markers, models, and mechanisms. Annu. Rev. Pathol. 2012, 7, 423-467.
Martinez-Outschoorn, U.E., Sotgia, F., Lisanti, M.P. Power surge: Supporting cells “fuel” cancer cell mitochondria. Cell Metab. 2012, 15, 4-5.
Kessenbrock, K., Plaks, V., Werb, Z. Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell 2010, 141, 52-67.
Taipale, J., Miyazono, K., Heldin, C.H., Keski-Oja, J. Latent transforming growth factor-β1 associates to fibroblast extracellular matrix via latent TGF-β binding protein. J. Cell Biol. 1994, 124, 171-181.
Lyons, R.M., Keski-Oja, J., Moses, H.L. Proteolytic activation of latent transforming growth factor-β from fibroblast-conditioned medium. J. Cell Biol. 1988, 106, 1659-1665.
Krstic, J., Santibanez, J.F. Transforming growth factor-β and matrix metalloproteinases: Functional interactions in tumor stroma-infiltrating myeloid cells. Sci. World J. 2014, 2014, 521754.
Gialeli, C., Theocharis, A.D., Karamanos, N.K. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J. 2011, 278, 16-27.
Egeblad, M., Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2002, 2, 161-174.
Gong, Y., Chippada-Venkata, U.D., Oh, W.K. Roles of matrix metalloproteinases and their natural inhibitors in prostate cancer progression. Cancers 2014, 6, 1298-1327.
D’Angelo, M., Billings, P.C., Pacifici, M., Leboy, P.S., Kirsch, T. Authentic matrix vesicles contain active metalloproteases (MMP). A role for matrix vesicle-associated MMP-13 in activation of transforming growth factor-β. J. Biol. Chem. 2001, 276, 11347-11353.
Ge, G., Greenspan, D.S. Bmp1 controls TGFβ1 activation via cleavage of latent TGFβ-binding protein. J. Cell Biol. 2006, 175, 111-120.
Maeda, S., Dean, D.D., Gomez, R., Schwartz, Z., Boyan, B.D. The first stage of transforming growth factor β1 activation is release of the large latent complex from the extracellular matrix of growth plate chondrocytes by matrix vesicle stromelysin-1 (MMP-3). Calcif. Tissue Int. 2002, 70, 54-65.
Mu, D., Cambier, S., Fjellbirkeland, L., Baron, J.L., Munger, J.S., Kawakatsu, H., Sheppard, D., Broaddus, V.C., Nishimura, S.L. The integrin α(v)β8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-β1. J. Cell Biol. 2002, 157, 493-507.
Yu, Q., Stamenkovic, I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-β and promotes tumor invasion and angiogenesis. Genes. Dev. 2000, 14, 163-176.
Dallas, S.L., Rosser, J.L., Mundy, G.R., Bonewald, L.F. Proteolysis of latent transforming growth factor-β (TGF-β)-binding protein-1 by osteoclasts. A cellular mechanism for release of TGF-β from bone matrix. J. Biol. Chem. 2002, 277, 21352-21360.
Tatti, O., Vehvilainen, P., Lehti, K., Keski-Oja, J. Mt1-MMP releases latent TGF-β1 from endothelial cell extracellular matrix via proteolytic processing of LTBP-1. Exp. Cell Res. 2008, 314, 2501-2514.
Dayer, C., Stamenkovic, I. Recruitment of matrix metalloproteinase-9 (MMP-9) to the fibroblast cell surface by lysyl hydroxylase 3 (LH3) triggers transforming growth factor-β (TGF-β) activation and fibroblast differentiation. J. Biol. Chem. 2015, 290, 13763-13778.
Desgrosellier, J.S., Cheresh, D.A. Integrins in cancer: Biological implications and therapeutic opportunities. Nat. Rev. Cancer 2010, 10, 9-22.
Wipff, P.J., Hinz, B. Integrins and the activation of latent transforming growth factor β1—An intimate relationship. Eur. J. Cell Biol. 2008, 87, 601-615.
Wipff, P.J., Rifkin, D.B., Meister, J.J., Hinz, B. Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix. J. Cell Biol. 2007, 179, 1311-1323.
Munger, J.S., Huang, X., Kawakatsu, H., Griffiths, M.J., Dalton, S.L., Wu, J., Pittet, J.F., Kaminski, N., Garat, C., Matthay, M.A., et al. The integrin αvβ6 binds and activates latent TGF β1: A mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999, 96, 319-328.
Reed, N.I., Jo, H., Chen, C., Tsujino, K., Arnold, T.D., DeGrado, W.F., Sheppard, D. The αvβ1 integrin plays a critical in vivo role in tissue fibrosis. Sci. Transl. Med. 2015, 7, 288ra279.
Asano, Y., Ihn, H., Yamane, K., Jinnin, M., Mimura, Y., Tamaki, K. Increased expression of integrin αvβ3 contributes to the establishment of autocrine TGF-β signaling in scleroderma fibroblasts. J. Immunol. 2005, 175, 7708-7718.
Asano, Y., Ihn, H., Yamane, K., Jinnin, M., Mimura, Y., Tamaki, K. Involvement of αvβ5 integrin-mediated activation of latent transforming growth factor β1 in autocrine transforming growth factor β signaling in systemic sclerosis fibroblasts. Arthritis Rheum. 2005, 52, 2897-2905.
Bonifazi, M., Tramacere, I., Pomponio, G., Gabrielli, B., Avvedimento, E.V., La Vecchia, C., Negri, E., Gabrielli, A. Systemic sclerosis (scleroderma) and cancer risk: Systematic review and meta-analysis of observational studies. Rheumatology 2013, 52, 143-154.
Krstic, J., Trivanovic, D., Mojsilovic, S., Santibanez, J.F. Transforming growth factor-β and oxidative stress interplay: Implications in tumorigenesis and cancer progression. Oxid. Med. Cell. Longev. 2015, 2015, 654594.
Sanjabi, S., Zenewicz, L.A., Kamanaka, M., Flavell, R.A. Anti-inflammatory and pro-inflammatory roles of TGF-β, IL-10, and IL-22 in immunity and autoimmunity. Curr. Opin. Pharmacol. 2009, 9, 447-453.
Barcellos-Hoff, M.H., Dix, T.A. Redox-mediated activation of latent transforming growth factor-β1. Mol. Endocrinol. 1996, 10, 1077-1083.
Ayala, G., Morello, M., Frolov, A., You, S., Li, R., Rosati, F., Bartolucci, G., Danza, G., Adam, R.M., Thompson, T.C., et al. Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression. J. Pathol. 2013, 231, 77-87.
Lee, E.K., Lee, Y.S., Han, I.O., Park, S.H. Expression of caveolin-1 reduces cellular responses to TGF-β 1 through down-regulating the expression of TGF-β type II receptor gene in NIH3T3 fibroblast cells. Biochem. Biophys. Res. Commun. 2007, 359, 385-390.
Jain, M., Rivera, S., Monclus, E.A., Synenki, L., Zirk, A., Eisenbart, J., Feghali-Bostwick, C., Mutlu, G.M., Budinger, G.R., Chandel, N.S. Mitochondrial reactive oxygen species regulate transforming growth factor-β signaling. J. Biol. Chem. 2013, 288, 770-777.
Jobling, M.F., Mott, J.D., Finnegan, M.T., Jurukovski, V., Erickson, A.C., Walian, P.J., Taylor, S.E., Ledbetter, S., Lawrence, C.M., Rifkin, D.B., et al. Isoform-specific activation of latent transforming growth factor β (LTGF-β) by reactive oxygen species. Radiat. Res. 2006, 166, 839-848.
Murphy-Ullrich, J.E., Poczatek, M. Activation of latent TGF-β by thrombospondin-1: Mechanisms and physiology. Cytokine Growth Factor Rev. 2000, 11, 59-69.
Schultz-Cherry, S., Ribeiro, S., Gentry, L., Murphy-Ullrich, J.E. Thrombospondin binds and activates the small and large forms of latent transforming growth factor-β in a chemically defined system. J. Biol. Chem. 1994, 269, 26775-26782.
Ribeiro, S.M., Poczatek, M., Schultz-Cherry, S., Villain, M., Murphy-Ullrich, J.E. The activation sequence of thrombospondin-1 interacts with the latency-associated peptide to regulate activation of latent transforming growth factor-β. J. Biol. Chem. 1999, 274, 13586-13593.
Crawford, S.E., Stellmach, V., Murphy-Ullrich, J.E., Ribeiro, S.M., Lawler, J., Hynes, R.O., Boivin, G.P., Bouck, N. Thrombospondin-1 is a major activator of TGF-β1 in vivo. Cell 1998, 93, 1159-1170.
Yehualaeshet, T., O’Connor, R., Green-Johnson, J., Mai, S., Silverstein, R., Murphy-Ullrich, J.E., Khalil, N. Activation of rat alveolar macrophage-derived latent transforming growth factor β-1 by plasmin requires interaction with thrombospondin-1 and its cell surface receptor, CD36. Am. J. Pathol. 1999, 155, 841-851.
Miyanaga, K., Kato, Y., Nakamura, T., Matsumura, M., Amaya, H., Horiuchi, T., Chiba, Y., Tanaka, K. Expression and role of thrombospondin-1 in colorectal cancer. Anticancer Res. 2002, 22, 3941-3948.
Kawataki, T., Naganuma, H., Sasaki, A., Yoshikawa, H., Tasaka, K., Nukui, H. Correlation of thrombospondin-1 and transforming growth factor-β expression with malignancy of glioma. Neuropathology 2000, 20, 161-169.
Dietz, H.C., Cutting, G.R., Pyeritz, R.E., Maslen, C.L., Sakai, L.Y., Corson, G.M., Puffenberger, E.G., Hamosh, A., Nanthakumar, E.J., Curristin, S.M., et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991, 352, 337-339.
Nistala, H., Lee-Arteaga, S., Smaldone, S., Siciliano, G., Carta, L., Ono, R.N., Sengle, G., Arteaga-Solis, E., Levasseur, R., Ducy, P., et al. Fibrillin-1 and-2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation. J. Cell Biol. 2010, 190, 1107-1121.
Ono, R.N., Sengle, G., Charbonneau, N.L., Carlberg, V., Bachinger, H.P., Sasaki, T., Lee-Arteaga, S., Zilberberg, L., Rifkin, D.B., Ramirez, F., et al. Latent transforming growth factor β-binding proteins and fibulins compete for fibrillin-1 and exhibit exquisite specificities in binding sites. J. Biol. Chem. 2009, 284, 16872-16881.
Sengle, G., Ono, R.N., Lyons, K.M., Bachinger, H.P., Sakai, L.Y. A new model for growth factor activation: Type II receptors compete with the prodomain for bmp-7. J. Mol. Biol. 2008, 381, 1025-1039.
Radice, P.D., Mathieu, P., Leal, M.C., Farias, M.I., Ferrari, C., Puntel, M., Salibe, M., Chernomoretz, A., Pitossi, F.J. Fibulin-2 is a key mediator of the pro-neurogenic effect of TGF-β1 on adult neural stem cells. Mol. Cell. Neurosci. 2015, 67, 75-83.
Sato, Y., Rifkin, D.B. Inhibition of endothelial cell movement by pericytes and smooth muscle cells: Activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J. Cell. Biol. 1989, 109, 309-315.
Blakytny, R., Ludlow, A., Martin, G.E., Ireland, G., Lund, L.R., Ferguson, M.W., Brunner, G. Latent TGF-β 1 activation by platelets. J. Cell Physiol. 2004, 199, 67-76.
Flaumenhaft, R., Abe, M., Sato, Y., Miyazono, K., Harpel, J., Heldin, C.H., Rifkin, D.B. Role of the latent TGF-β binding protein in the activation of latent TGF-β by co-cultures of endothelial and smooth muscle cells. J. Cell. Biol. 1993, 120, 995-1002.
Antonelli-Orlidge, A., Saunders, K.B., Smith, S.R., D’Amore, P.A. An activated form of transforming growth factor β is produced by cocultures of endothelial cells and pericytes. Proc. Natl. Acad. Sci. USA 1989, 86, 4544-4548.
Paget, S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989, 8, 98-101.
Stylianopoulos, T., Martin, J.D., Chauhan, V.P., Jain, S.R., Diop-Frimpong, B., Bardeesy, N., Smith, B.L., Ferrone, C.R., Hornicek, F.J., Boucher, Y., et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc. Natl. Acad. Sci. USA 2012, 109, 15101-15108.
Kalamajski, S., Oldberg, A. The role of small leucine-rich proteoglycans in collagen fibrillogenesis. Matrix Biol. 2010, 29, 248-253.
Grant, D.S., Yenisey, C., Rose, R.W., Tootell, M., Santra, M., Iozzo, R.V. Decorin suppresses tumor cell-mediated angiogenesis. Oncogene 2002, 21, 4765-4777.
Troup, S., Njue, C., Kliewer, E.V., Parisien, M., Roskelley, C., Chakravarti, S., Roughley, P.J., Murphy, L.C., Watson, P.H. Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer. Clin. Cancer Res. 2003, 9, 207-214.
Baghy, K., Dezso, K., Laszlo, V., Fullar, A., Peterfia, B., Paku, S., Nagy, P., Schaff, Z., Iozzo, R.V., Kovalszky, I. Ablation of the decorin gene enhances experimental hepatic fibrosis and impairs hepatic healing in mice. Lab. Investig. 2011, 91, 439-451.
Abdel-Wahab, N., Wicks, S.J., Mason, R.M., Chantry, A. Decorin suppresses transforming growth factor-β-induced expression of plasminogen activator inhibitor-1 in human mesangial cells through a mechanism that involves Ca2+-dependent phosphorylation of Smad2 at serine-240. Biochem. J. 2002, 362, 643-649.
Stander, M., Naumann, U., Dumitrescu, L., Heneka, M., Loschmann, P., Gulbins, E., Dichgans, J., Weller, M. Decorin gene transfer-mediated suppression of TGF-β synthesis abrogates experimental malignant glioma growth in vivo. Gene. Ther. 1998, 5, 1187-1194.
Biglari, A., Bataille, D., Naumann, U., Weller, M., Zirger, J., Castro, M.G., Lowenstein, P.R. Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model. Cancer Gene Ther. 2004, 11, 721-732.
Merline, R., Moreth, K., Beckmann, J., Nastase, M.V., Zeng-Brouwers, J., Tralhao, J.G., Lemarchand, P., Pfeilschifter, J., Schaefer, R.M., Iozzo, R.V., et al. Signaling by the matrix proteoglycan decorin controls inflammation and cancer through pdcd4 and microrna-21. Sci. Signal. 2011, 4, 75.
Hildebrand, A., Romaris, M., Rasmussen, L.M., Heinegard, D., Twardzik, D.R., Border, W.A., Ruoslahti, E. Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor β. Biochem. J. 1994, 302, 527-534.
Mochida, Y., Parisuthiman, D., Yamauchi, M. Biglycan is a positive modulator of BMP-2 induced osteoblast differentiation. Adv. Exp. Med. Biol. 2006, 585, 101-113.
Kolb, M., Margetts, P.J., Sime, P.J., Gauldie, J. Proteoglycans decorin and biglycan differentially modulate TGF-β-mediated fibrotic responses in the lung. Am. J. Physiol. Lung Cell Mol. Physiol. 2001, 280, L1327-L1334.
Westergren-Thorsson, G., Antonsson, P., Malmstrom, A., Heinegard, D., Oldberg, A. The synthesis of a family of structurally related proteoglycans in fibroblasts is differently regulated by TFG-β. Matrix 1991, 11, 177-183.
Schmidt, M., Bohm, D., von Torne, C., Steiner, E., Puhl, A., Pilch, H., Lehr, H.A., Hengstler, J.G., Kolbl, H., Gehrmann, M. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res. 2008, 68, 5405-5413.
Desmedt, C., Piette, F., Loi, S., Wang, Y., Lallemand, F., Haibe-Kains, B., Viale, G., Delorenzi, M., Zhang, Y., d’Assignies, M.S., et al. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the transbig multicenter independent validation series. Clin. Cancer Res. 2007, 13, 3207-3214.
LaTulippe, E., Satagopan, J., Smith, A., Scher, H., Scardino, P., Reuter, V., Gerald, W.L. Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res. 2002, 62, 4499-4506.
Lee, Y.H., Schiemann, W.P. Fibromodulin suppresses nuclear factor-kappab activity by inducing the delayed degradation of ikba via a jnk-dependent pathway coupled to fibroblast apoptosis. J. Biol. Chem. 2011, 286, 6414-6422.
Fukushima, D., Butzow, R., Hildebrand, A., Ruoslahti, E. Localization of transforming growth factor β binding site in betaglycan. Comparison with small extracellular matrix proteoglycans. J. Biol. Chem. 1993, 268, 22710-22715.
Zheng, Z., Nguyen, C., Zhang, X., Khorasani, H., Wang, J.Z., Zara, J.N., Chu, F., Yin, W., Pang, S., Le, A., et al. Delayed wound closure in fibromodulin-deficient mice is associated with increased TGF-β 3 signaling. J. Investig. Dermatol. 2011, 131, 769-778.
Adini, I., Ghosh, K., Adini, A., Chi, Z.L., Yoshimura, T., Benny, O., Connor, K.M., Rogers, M.S., Bazinet, L., Birsner, A.E., et al. Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment. J. Clin. Investig. 2014, 124, 425-436.
Maris, P., Blomme, A., Palacios, A.P., Costanza, B., Bellahcene, A., Bianchi, E., Gofflot, S., Drion, P., Trombino, G.E., Di Valentin, E., et al. Asporin is a fibroblast-derived TGF-β1 inhibitor and a tumor suppressor associated with good prognosis in breast cancer. PLoS Med. 2015, 12, e1001871.
Satoyoshi, R., Kuriyama, S., Aiba, N., Yashiro, M., Tanaka, M. Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. Oncogene 2015, 34, 650-660.
Kou, I., Nakajima, M., Ikegawa, S. Binding characteristics of the osteoarthritis-associated protein asporin. J. Bone Miner. Metab 2010, 28, 395-402.
Ishiwata, T., Cho, K., Kawahara, K., Yamamoto, T., Fujiwara, Y., Uchida, E., Tajiri, T., Naito, Z. Role of lumican in cancer cells and adjacent stromal tissues in human pancreatic cancer. Oncol. Rep. 2007, 18, 537-543.
Leygue, E., Snell, L., Dotzlaw, H., Hole, K., Hiller-Hitchcock, T., Roughley, P.J., Watson, P.H., Murphy, L.C. Expression of lumican in human breast carcinoma. Cancer Res. 1998, 58, 1348-1352.
Nikitovic, D., Berdiaki, A., Zafiropoulos, A., Katonis, P., Tsatsakis, A., Karamanos, N.K., Tzanakakis, G.N. Lumican expression is positively correlated with the differentiation and negatively with the growth of human osteosarcoma cells. FEBS J. 2008, 275, 350-361.
Kao, W.W. Ocular surface tissue morphogenesis in normal and disease states revealed by genetically modified mice. Cornea 2006, 25, S7-S19.
Mochida, Y., Parisuthiman, D., Kaku, M., Hanai, J., Sukhatme, V.P., Yamauchi, M. Nephrocan, a novel member of the small leucine-rich repeat protein family, is an inhibitor of transforming growth factor-beta signaling. J. Biol. Chem. 2006, 281, 36044-36051.
Kielty, C.M., Wess, T.J., Haston, L., Ashworth, J.L., Sherratt, M.J., Shuttleworth, C.A. Fibrillin-rich microfibrils: Elastic biopolymers of the extracellular matrix. J. Muscle Res. Cell Motil. 2002, 23, 581-596.
Kaartinen, V., Warburton, D. Fibrillin controls TGF-β activation. Nat. Genet. 2003, 33, 331-332.
Lind, G.E., Danielsen, S.A., Ahlquist, T., Merok, M.A., Andresen, K., Skotheim, R.I., Hektoen, M., Rognum, T.O., Meling, G.I., Hoff, G., et al. Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas. Mol. Cancer 2011, 10, 85.
Guo, Q., Song, Y., Zhang, H., Wu, X., Xia, P., Dang, C. Detection of hypermethylated fibrillin-1 in the stool samples of colorectal cancer patients. Med. Oncol. 2013, 30, 695.
Hellebrekers, D.M., Melotte, V., Vire, E., Langenkamp, E., Molema, G., Fuks, F., Herman, J.G., Van Criekinge, W., Griffioen, A.W., van Engeland, M. Identification of epigenetically silenced genes in tumor endothelial cells. Cancer Res. 2007, 67, 4138-4148.
Kim, E.J., Lee, S.Y., Woo, M.K., Choi, S.I., Kim, T.R., Kim, M.J., Kim, K.C., Cho, E.W., Kim, I.G. Fibulin-3 promoter methylation alters the invasive behavior of non-small cell lung cancer cell lines via MMP-7 and MMP-2 regulation. Int. J. Oncol. 2012, 40, 402-408.
Wang, Z., Yuan, X., Jiao, N., Zhu, H., Zhang, Y., Tong, J. Cdh13 and flbn3 gene methylation are associated with poor prognosis in colorectal cancer. Pathol. Oncol. Res. 2012, 18, 263-270.
Tian, H., Liu, J., Chen, J., Gatza, M.L., Blobe, G.C. Fibulin-3 is a novel TGF-β pathway inhibitor in the breast cancer microenvironment. Oncogene 2015, 34, 5635-5647.
Tong, J.D., Jiao, N.L., Wang, Y.X., Zhang, Y.W., Han, F. Downregulation of fibulin-3 gene by promoter methylation in colorectal cancer predicts adverse prognosis. Neoplasma 2011, 58, 441-448.
Wang, R., Zhang, Y.W., Chen, L.B. Aberrant promoter methylation of fbln-3 gene and clinicopathological significance in non-small cell lung carcinoma. Lung Cancer 2010, 69, 239-244.
Nomoto, S., Kanda, M., Okamura, Y., Nishikawa, Y., Li, Q., Fujii, T., Sugimoto, H., Takeda, S., Nakao, A. Epidermal growth factor-containing fibulin-like extracellular matrix protein 1, efemp1, a novel tumor-suppressor gene detected in hepatocellular carcinoma using double combination array analysis. Ann. Surg. Oncol. 2010, 17, 923-932.
Renard, M., Holm, T., Veith, R., Callewaert, B.L., Ades, L.C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., et al. Altered TGFβ signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type i caused by fibulin-4 deficiency. Eur J. Hum. Genet. 2010, 18, 895-901.
Huang, J., Davis, E.C., Chapman, S.L., Budatha, M., Marmorstein, L.Y., Word, R.A., Yanagisawa, H. Fibulin-4 deficiency results in ascending aortic aneurysms: A potential link between abnormal smooth muscle cell phenotype and aneurysm progression. Circ. Res. 2010, 106, 583-592.
Johnson, K.J., Sage, H., Briscoe, G., Erickson, H.P. The compact conformation of fibronectin is determined by intramolecular ionic interactions. J. Biol. Chem. 1999, 274, 15473-15479.
Williams, C.M., Engler, A.J., Slone, R.D., Galante, L.L., Schwarzbauer, J.E. Fibronectin expression modulates mammary epithelial cell proliferation during acinar differentiation. Cancer Res. 2008, 68, 3185-3192.
Dallas, S.L., Sivakumar, P., Jones, C.J., Chen, Q., Peters, D.M., Mosher, D.F., Humphries, M.J., Kielty, C.M. Fibronectin regulates latent transforming growth factor-β (TGFβ) by controlling matrix assembly of latent TGFβ-binding protein-1. J. Biol. Chem. 2005, 280, 18871-18880.
Ignotz, R.A., Massague, J. Transforming growth factor-β stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J. Biol. Chem. 1986, 261, 4337-4345.
Collo, G., Pepper, M.S. Endothelial cell integrin α5β1 expression is modulated by cytokines and during migration in vitro. J. Cell Sci. 1999, 112, 569-578.
Akhurst, R.J., Hata, A. Targeting the TGFβ signalling pathway in disease. Nat. Rev. Drug Discov. 2012, 11, 790-811.
Connolly, E.C., Freimuth, J., Akhurst, R.J. Complexities of TGF-β targeted cancer therapy. Int. J. Biol. Sci. 2012, 8, 964-978.
Saunier, E.F., Akhurst, R.J. TGFβ inhibition for cancer therapy. Curr. Cancer Drug Targets 2006, 6, 565-578.
Seoane, J. The TGFβ pathway as a therapeutic target in cancer. Clin. Transl. Oncol. 2008, 10, 14-19.
Tralhao, J.G., Schaefer, L., Micegova, M., Evaristo, C., Schonherr, E., Kayal, S., Veiga-Fernandes, H., Danel, C., Iozzo, R.V., Kresse, H., et al. In vivo selective and distant killing of cancer cells using adenovirus-mediated decorin gene transfer. FASEB J. 2003, 17, 464-466.
Rasmussen, H.S., McCann, P.P. Matrix metalloproteinase inhibition as a novel anticancer strategy: A review with special focus on batimastat and marimastat. Pharmacol. Ther. 1997, 75, 69-75.
Bramhall, S.R., Rosemurgy, A., Brown, P.D., Bowry, C., Buckels, J.A. Marimastat as first-line therapy for patients with unresectable pancreatic cancer: A randomized trial. J. Clin. Oncol. 2001, 19, 3447-3455.
Levitt, N.C., Eskens, F.A., O’Byrne, K.J., Propper, D.J., Denis, L.J., Owen, S.J., Choi, L., Foekens, J.A., Wilner, S., Wood, J.M., et al. Phase i and pharmacological study of the oral matrix metalloproteinase inhibitor, MMI270 (CGS27023A), in patients with advanced solid cancer. Clin. Cancer Res. 2001, 7, 1912-1922.
Bissett, D., O’Byrne, K.J., von Pawel, J., Gatzemeier, U., Price, A., Nicolson, M., Mercier, R., Mazabel, E., Penning, C., Zhang, M.H., et al. Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J. Clin. Oncol. 2005, 23, 842-849.
Hirte, H., Vergote, I.B., Jeffrey, J.R., Grimshaw, R.N., Coppieters, S., Schwartz, B., Tu, D., Sadura, A., Brundage, M., Seymour, L. A phase III randomized trial of bay 12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy: A national cancer institute of canada clinical trials group study. Gynecol. Oncol. 2006, 102, 300-308.
Leighl, N.B., Paz-Ares, L., Douillard, J.Y., Peschel, C., Arnold, A., Depierre, A., Santoro, A., Betticher, D.C., Gatzemeier, U., Jassem, J., et al. Randomized phase iii study of matrix metalloproteinase inhibitor bms-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute Of Canada-Clinical Trials Group Study BR.18. J. Clin. Oncol. 2005, 23, 2831-2839.
Syed, S., Takimoto, C., Hidalgo, M., Rizzo, J., Kuhn, J.G., Hammond, L.A., Schwartz, G., Tolcher, A., Patnaik, A., Eckhardt, S.G., et al. A phase i and pharmacokinetic study of Col-3 (Metastat), an oral tetracycline derivative with potent matrix metalloproteinase and antitumor properties. Clin. Cancer Res. 2004, 10, 6512-6521.
Duivenvoorden, W.C., Popovic, S.V., Lhotak, S., Seidlitz, E., Hirte, H.W., Tozer, R.G., Singh, G. Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer. Cancer Res. 2002, 62, 1588-1591.
Hersey, P., Sosman, J., O’Day, S., Richards, J., Bedikian, A., Gonzalez, R., Sharfman, W., Weber, R., Logan, T., Buzoianu, M., et al. A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, β dacarbazine in patients with stage IV metastatic melanoma. Cancer 2010, 116, 1526-1534.
Heidenreich, A., Rawal, S.K., Szkarlat, K., Bogdanova, N., Dirix, L., Stenzl, A., Welslau, M., Wang, G., Dawkins, F., de Boer, C.J., et al. A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human alphanu integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer. Ann. Oncol. 2013, 24, 329-336.
Stupp, R., Hegi, M.E., Gorlia, T., Erridge, S.C., Perry, J., Hong, Y.K., Aldape, K.D., Lhermitte, B., Pietsch, T., Grujicic, D., et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated mgmt promoter (centric eortc 26071-22072 study): A multicentre, randomised, open-label, phase 3 trial. Lancet. Oncol. 2014, 15, 1100-1108.
Infante, J.R., Camidge, D.R., Mileshkin, L.R., Chen, E.X., Hicks, R.J., Rischin, D., Fingert, H., Pierce, K.J., Xu, H., Roberts, W.G., et al. Safety, pharmacokinetic, and pharmacodynamic phase i dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors. J. Clin. Oncol. 2012, 30, 1527-1533.
Tanjoni, I., Walsh, C., Uryu, S., Tomar, A., Nam, J.O., Mielgo, A., Lim, S.T., Liang, C., Koenig, M., Sun, C., et al. PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments. Cancer Biol. Ther. 2010, 9, 764-777.
Cathcart, J., Pulkoski-Gross, A., Cao, J. Targeting matrix metalloproteinases in cancer: Bringing new life to old ideas. Genes Dis. 2015, 2, 26-34.
Liu, J., Xiong, W., Baca-Regen, L., Nagase, H., Baxter, B.T. Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells. J. Vasc. Surg. 2003, 38, 1376-1383.
Son, K., Fujioka, S., Iida, T., Furukawa, K., Fujita, T., Yamada, H., Chiao, P.J., Yanaga, K. Doxycycline induces apoptosis in panc-1 pancreatic cancer cells. Anticancer Res. 2009, 29, 3995-4003.
Lamb, R., Ozsvari, B., Lisanti, C.L., Tanowitz, H.B., Howell, A., Martinez-Outschoorn, U.E., Sotgia, F., Lisanti, M.P. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease. Oncotarget 2015, 6, 4569-4584.
Delbaldo, C., Raymond, E., Vera, K., Hammershaimb, L., Kaucic, K., Lozahic, S., Marty, M., Faivre, S. Phase i and pharmacokinetic study of etaracizumab (abegrin), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors. Investig. New Drugs 2008, 26, 35-43.
Salvo, E., Garasa, S., Dotor, J., Morales, X., Pelaez, R., Altevogt, P., Rouzaut, A. Combined targeting of TGF-β1 and integrin β3 impairs lymph node metastasis in a mouse model of non-small-cell lung cancer. Mol. Cancer 2014, 13, 112.
O’Day, S., Pavlick, A., Loquai, C., Lawson, D., Gutzmer, R., Richards, J., Schadendorf, D., Thompson, J.A., Gonzalez, R., Trefzer, U., et al. A randomised, phase ii study of intetumumab, an anti-alphav-integrin mab, alone and with dacarbazine in stage iv melanoma. Br. J. Cancer 2011, 105, 346-352.
Reardon, D.A., Fink, K.L., Mikkelsen, T., Cloughesy, T.F., O’Neill, A., Plotkin, S., Glantz, M., Ravin, P., Raizer, J.J., Rich, K.M., et al. Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastomamultiforme. J. Clin. Oncol. 2008, 26, 5610-5617.
Danen, E.H., Lafrenie, R.M., Miyamoto, S., Yamada, K.M. Integrin signaling: Cytoskeletal complexes, MAP kinase activation, and regulation of gene expression. Cell Adhes. Commun. 1998, 6, 217-224.
Kaspar, M., Zardi, L., Neri, D. Fibronectin as target for tumor therapy. Int. J. Cancer 2006, 118, 1331-1339.
Santimaria, M., Moscatelli, G., Viale, G.L., Giovannoni, L., Neri, G., Viti, F., Leprini, A., Borsi, L., Castellani, P., Zardi, L., et al. Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer. Clin. Cancer Res. 2003, 9, 571-579.
Fabbrini, M., Trachsel, E., Soldani, P., Bindi, S., Alessi, P., Bracci, L., Kosmehl, H., Zardi, L., Neri, D., Neri, P. Selective occlusion of tumor blood vessels by targeted delivery of an antibody-photosensitizer conjugate. Int. J. Cancer 2006, 118, 1805-1813.
Carnemolla, B., Borsi, L., Balza, E., Castellani, P., Meazza, R., Berndt, A., Ferrini, S., Kosmehl, H., Neri, D., Zardi, L. Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix. Blood 2002, 99, 1659-1665.
Borsi, L., Balza, E., Carnemolla, B., Sassi, F., Castellani, P., Berndt, A., Kosmehl, H., Biro, A., Siri, A., Orecchia, P., et al. Selective targeted delivery of TNFβ to tumor blood vessels. Blood 2003, 102, 4384-4392.
Danielli, R., Patuzzo, R., Di Giacomo, A.M., Gallino, G., Maurichi, A., Di Florio, A., Cutaia, O., Lazzeri, A., Fazio, C., Miracco, C., et al. Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a melanoma patients: Results of a phase II study. Cancer Immunol. Immunother. 2015, 64, 999-1009.
Ishikawa, T., Kokura, S., Enoki, T., Sakamoto, N., Okayama, T., Ideno, M., Mineno, J., Uno, K., Yoshida, N., Kamada, K., et al. Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer. PLoS ONE 2014, 9, e83786.