References of "Castronovo, Vincenzo"
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See detailCartilage as a Source of Natural Inhibitors of Angiogenesis.
Castronovo, Vincenzo ULg; Dimitriadou, V.; Savard, P. et al

in Antiangiogenic Agents in Cancer Therapy. (1999)

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See detailGalectin-1 Expression in Prostate Tumor-Associated Capillary Endothelial Cells Is Increased by Prostate Carcinoma Cells and Modulates Heterotypic Cell-Cell Adhesion
Clausse, Nathalie; van den Brule, Frédéric; Waltregny, David ULg et al

in Angiogenesis (1999), 3(4), 317-25

Besides providing tumors with nutrients, newly formed capillaries constitute a potential escape route for tumor cells favoring metastatic dissemination, and constitute an access for the anti-tumoral host ... [more ▼]

Besides providing tumors with nutrients, newly formed capillaries constitute a potential escape route for tumor cells favoring metastatic dissemination, and constitute an access for the anti-tumoral host immune cells. Galectin-1, a soluble human lectin, is involved in numerous biological functions including cell-cell and cell-substrate interactions. In addition, galectin-1 is able to induce apoptosis of activated T-lymphocytes. In this study, we have examined galectin-1 expression in capillaries associated to the carcinoma cells or present in the remote non-tumoral stroma of 100 human prostate carcinoma samples by immunoperoxidase staining. Galectin-1 was expressed by endothelial cells from capillaries infiltrating the tumor tissue in 64% (64/100) of the cases. On the contrary, endothelial cells in the adjacent non-tumoral stroma expressed galectin-1 in very few cases (7/100). Increased frequency of galectin-1-positive capillaries in the tumor-associated compared to the tumor-free areas was observed in 63% of the cases. This striking contrast led us to set up an in vitro model to test whether tumor cells could induce galectin-1 expression by endothelial cells. Incubation of human umbilical vein endothelial cells with conditioned media from PC-3 or DU 145 prostate carcinoma cells led to a significant increase of galectin-1 protein expression (+32.97% and 37.91% P < 0.01 and P < 0.05, respectively). PC-3 conditioned medium also induced increased adhesion values of PC-3 cells to the endothelial cells (53.4 +/- 4.7 vs. 38.5 +/- 3.5 after 30 min; 66.6 +/- 7.8 vs. 46.2 +/- 6.4 after 60 min). An anti-galectin-1 antiserum abolished this modulation, and recombinant galectin-1 also induced increased adhesion values in a dose-dependent fashion. This effect was specific as no such modulations were observed using normal lymphocytes instead of PC-3 cells. Preferential galectin-1 expression in the endothelial cells close to the cancer cells could provide these latter with increased abilities to interact with the endothelial cells as well as a defense against the host immune system. [less ▲]

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See detailTnf-Alpha and Ifn-Gamma Down-Regulate the Expression of the Metastasis-Associated Bi-Functional 37lrp/P40 Gene and Protein in Transformed Keratinocytes
Clausse, Nathalie; van den Brûle, Frédéric; Delvenne, Philippe ULg et al

in Biochemical and Biophysical Research Communications (1998), 251(2), 564-9

The 37 LRP/p40 molecule is a bi-functional protein in which expression is increased in a large variety of cancers in association with their metastatic phenotype. Here we present the first data concerning ... [more ▼]

The 37 LRP/p40 molecule is a bi-functional protein in which expression is increased in a large variety of cancers in association with their metastatic phenotype. Here we present the first data concerning the 37 LRP/p40 gene promoter activity and show that it is very active in a cervix carcinoma cell line. Interestingly, despite hallmarks of a housekeeping gene, we show that the 37 LRP/p40 gene promoter can be down-regulated by two potentially anticancerous cytokines, TNF-alpha and IFN-gamma. In addition, the dual fate of the protein, i.e., being intracellularly involved in the cell translation machinery and incorporated into a 67-kDa cell surface protein functioning as a laminin receptor (67LR), is differentially affected by the treatment. Our data suggest multiple regulation levels in the control of the 67LR/37LRP/p40 molecule expression and uncover new clues for the understanding of both the control of expression of this metastasis-associated molecule and the IFN-gamma and TNF-alpha anticancerous action. [less ▲]

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See detailMolecular Cloning of a Mutated Hoxb7 Cdna Encoding a Truncated Transactivating Homeodomain-Containing Protein
Chariot, Alain ULg; Senterre-Lesenfants, Sylviane; Sobel, Mark E et al

in Journal of Cellular Biochemistry (1998), 71(1), 46-54

Homeodomain-containing proteins regulate, as transcription factors, the coordinated expression of genes involved in development, differentiation, and malignant transformation. We report here the molecular ... [more ▼]

Homeodomain-containing proteins regulate, as transcription factors, the coordinated expression of genes involved in development, differentiation, and malignant transformation. We report here the molecular cloning of a mutated HOXB7 transcript encoding a truncated homeodomain-containing protein in MCF7 cells. This is a new example of mutation affecting the coding region of a HOX gene. In addition, we detected two HOXB7 transcripts in several breast cell lines and demonstrated that both normal and mutated alleles were expressed at the RNA level in MCF7 cells as well as in a variety of breast tissues and lymphocytes, suggesting that a truncated HOXB7 protein might be expressed in vivo. Using transient co-transfection experiments, we demonstrated that both HOXB7 proteins can activate transcription from a consensus HOX binding sequence in breast cancer cells. Our results provide evidence that HOXB7 protein has transcription factor activity in vivo and that the two last amino acids do not contribute to this property. [less ▲]

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See detailExpression and Modulation of Homeobox Genes from Cluster B in Endothelial Cells
Belotti, D.; Clausse, Nathalie; Flagiello, D. et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (1998), 78(10), 1291-9

Angiogenesis is a complex phenomenon likely to be under the strict control of a group of transcription factor(s). Homeobox (HOX)-containing proteins have been identified as regulators controlling the ... [more ▼]

Angiogenesis is a complex phenomenon likely to be under the strict control of a group of transcription factor(s). Homeobox (HOX)-containing proteins have been identified as regulators controlling the coordinated expression of genes involved in organ development and tissue differentiation. In this study, we have demonstrated that human umbilical vein endothelial cells (HUVEC) express 8 of the 10 HOX genes contained in cluster B. Treatment of HUVEC with tissue plasminogen activator (TPA), an agent known to induce morphologic changes in endothelial cells, or vascular endothelium growth factor (VEGF), a proliferative and angiogenesis inducer, results in a specific time-dependent modulation of the eight HOX genes identified. Interestingly, neither basic fibroblast growth factor, an endothelial proliferative agent, nor TNP-470, a fumagillin derivative with potent antiendothelial cell proliferation properties, affected expression of these HOX genes. Specific modulation of HOX genes by differentiating agents but not by proliferative or antiproliferative molecules suggests that they could be involved in the control of the genetic program that coordinates the construction of new blood vessels. [less ▲]

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See detailTransglutaminase-Mediated Oligomerization of Galectin-3 Modulates Human Melanoma Cell Interactions with Laminin
van den Brule, F. A.; Liu, F. T.; Castronovo, Vincenzo ULg

in Cell Adhesion and Communication (1998), 5(6), 425-35

Tumor cell adhesion and migration to laminin are important events during invasion and metastatic spread. Galectin-3, a multifunctional member of the galectin family, binds specifically the poly-N ... [more ▼]

Tumor cell adhesion and migration to laminin are important events during invasion and metastatic spread. Galectin-3, a multifunctional member of the galectin family, binds specifically the poly-N-acetyllactosamine residues of laminin and has been implicated in tumor invasion and metastasis. Galectin-3 is multimerized by transglutaminase, an enzyme that catalyzes cross-linking between glutamine and other aminoacid residues. In this study, we examined the consequences of transglutaminase-mediated galectin-3 oligomerization on the interactions between cancer cells and laminin. We first demonstrated that human galectin-3 is cross-linked by guinea pig liver transglutaminase, forms oligomers, and incorporates the marker 5-(biotinamido) pentylamine. Expression of transglutaminase activity in the A375 and A2058 human melanoma cell extracts was revealed by its ability to induce galectin-3 oligomerization and 5-(biotinamido) pentylamine incorporation. Transglutaminase-treated galectin-3 did not affect adhesion or migration of the melanoma cells to laminin but consistently induced a significant increase of the percentage of cell spreading compared to the control (23.5 +/- 2.3%, vs. 10.6 +/- 1.9% at 180 min, p < 0.05), or to untreated galectin-3 or transglutaminase alone. Our study is the first demonstration that human galectin-3 is oligomerized by transglutaminase with, as a consequence, a specific effect of melanoma cell spreading on laminin. This phenomenon could be of significance in the modulation of cancer cell interactions with laminin during tumor invasion and metastasis. [less ▲]

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See detailEctopic Expression of Bone Sialoprotein in Human Thyroid Cancer
Bellahcene, Akeila ULg; Albert, V.; Pollina, L. et al

in Thyroid (1998), 8(8), 637-41

Bone sialoprotein (BSP) is a small, highly posttranslationally modified integrin binding protein found in the mineral compartment of developing bone. The recent discovery that BSP can be detected in a ... [more ▼]

Bone sialoprotein (BSP) is a small, highly posttranslationally modified integrin binding protein found in the mineral compartment of developing bone. The recent discovery that BSP can be detected in a variety of human cancers, particularly those that metastasize preferentially to the skeleton, shed light on potential new biological functions for this protein. The demonstration of a positive association between BSP expression in primary breast tumors and the development of bone metastases suggests that this glycoprotein could play a role in the selective implantation of breast cancer cells in bone. BSP is also expressed in most lung and prostate cancers as well as in multiple myeloma, three other osteotropic malignancies. Because thyroid carcinoma also metastasizes preferentially to the skeleton, we decided to look at the expression of BSP in a collection of 145 thyroid malignant lesions including 24 follicular thyroid carcinomas (FTCs), 55 papillary thyroid carcinomas (PTCs), 19 medullary thyroid carcinomas (MTCs), 23 anaplastic carcinomas (ACs), and 24 poorly differentiated carcinomas (PDCs). BSP expression was evaluated by immunoperoxidase technique using two specific polyclonal antibodies. Most of the thyroid carcinomas (72%) examined expressed high levels of BSP. Expression of BSP was significantly lower in FTCs and MTCs compared with PDCs, which are more aggressive (p = 0.0009 and 0.0003, respectively). Our study demonstrates for the first time that ectopic BSP expression is a common feature of thyroid cancer. The prognostic value of BSP detection in thyroid adenocarcinoma and the potential role of BSP in the propension of this type of cancer to metastasize to bone are currently under investigation. [less ▲]

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See detailPrognostic Value of Bone Sialoprotein Expression in Clinically Localized Human Prostate Cancer
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

in Journal of the National Cancer Institute (1998), 90(13), 1000-8

BACKGROUND: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the ... [more ▼]

BACKGROUND: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the development of bone metastases in that disease. These data prompted us to investigate whether BSP might also be expressed in human prostate cancer, which often metastasizes to bone, and be predictive for progression risk. METHODS: Tissue sections from 180 patients who had undergone a radical prostatectomy for localized prostate cancer were analyzed immunohistochemically for BSP expression. Biochemical progression was defined as an increasing serum prostate-specific antigen level of 0.5 ng/mL or more. Statistical analysis was used to assess associations between pathologic findings and level of BSP expression, and a Cox proportional hazards model was used to determine which clinical and histologic parameters, including stage, Gleason score, and BSP expression (immunostaining intensity and extent), were independently associated with biochemical progression. All P values were two-sided. RESULTS: Most of the prostate cancer lesions examined (78.9%) expressed detectable levels of BSP, compared with no or low expression in the adjacent normal glandular tissue. A statistically significant association was found between BSP expression and biochemical progression in both univariate and multivariate analyses. After a follow-up interval of 3 years, the biochemical relapse rate was 36.7% (95% confidence interval [CI] = 23.4%-47.7%) in patients whose tumors expressed high levels of BSP compared with 12.1% (95% CI = 2.3%-20.8%) in patients whose tumors expressed no or a low detectable level of the protein (logrank test, P = .0014). BSP expression status could identify those patients at higher risk of biochemical progression (logrank test, P<.05) among patients with moderately differentiated tumors or with pathologically confined tumors. CONCLUSIONS: To our knowledge, this study is the first to demonstrate BSP expression in human prostate cancer and to highlight the protein's statistically significant prognostic value in patients with clinically confined prostate adenocarcinomas. [less ▲]

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See detailCancer du col de l'utérus: analyse du coût-bénéfice et de l'efficacité du dépistage opportuniste versus le dépistage organisé
Castronovo, Vincenzo ULg; Foidart, Jean-Michel ULg; Boniver, Jacques ULg

in Revue Médicale de Liège (1998), 53(5), 305-7

Cervical cancer is the fourth cancer in women. It is the first malignancy for which mass population screening has been demonstrated to significantly reduce the mortality due to this disease. In Belgium ... [more ▼]

Cervical cancer is the fourth cancer in women. It is the first malignancy for which mass population screening has been demonstrated to significantly reduce the mortality due to this disease. In Belgium, the mortality associated to cervical cancer decreased from 6 to 4 per 100,000 women-years from 1955-1959 to 1985-1989. European recommendations regarding cervical cancer screening are to perform a cervical smear each three years in women aged 25 to 65 years. In Belgium, while the Flemish region has decided to organize the cervical cancer screening according to the European recommendations, the screening in the French part of the country is essentially opportunistic. In this short review, the cost/benefit of the organized screening versus the opportunistic screening is discussed. [less ▲]

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See detailEvidence That Breast Cancer Associated Microcalcifications Are Mineralized Malignant Cells
Castronovo, Vincenzo ULg; Bellahcene, Akeila ULg

in International Journal of Oncology (1998), 12(2), 305-8

Microcalcifications are often associated with both benign and malignant human breast lesions. Around 40% of mammary carcinoma present such ectopic mineralization and frequently, they are the only ... [more ▼]

Microcalcifications are often associated with both benign and malignant human breast lesions. Around 40% of mammary carcinoma present such ectopic mineralization and frequently, they are the only mammographic feature that indicate the presence of a tumoral lesion. Microcalcifications associated with breast cancer are usually composed of hydroxyapatite, the bone specific mineral. The mechanisms responsible for the formation of such crystals within breast malignant tissue have not been elucidated. A possible clue could be provided by the recent demonstration that breast cancer cells express several bone matrix proteins including osteonectin, osteopontin and bone sialoprotein (BSP). This latter phospho-protein is involved in the initiation of hydroxyapatite crystallisation and its expression in breast cancer has been associated to the presence of hydroxyapatite microcalcifications. We examined 10 human breast cancer lesions which were characterized by the presence of microcalcifications and high expression of BSP. Histological examination of the lesions suggested, in most of the cases, that the microcalcifications were breast cancer cells which became mineralized. Hydroxyapatite stained in blue by hematoxylin appears concentrated around single of associated cancer cells. Staining of these tissue sections with 4',6 diamidino-2-phenylindole which specifically labels DNA led us to demonstrate that the mineralizated structures contain cells. These data are the first direct demonstration that breast microcalcifications are fossils of cancer cells. The mechanisms for such a phenomenon remain to be demonstrated. We speculate that the high expression of BSP could create an appropriate microenvironment for the crystallisation of calcium and phosphate into hydroxyapatite. [less ▲]

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See detailExpression of bone sialoprotein in human prostate is associated with progression
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

Conference (1998, January 23)

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See detailExpression of bone sialoprotein in human prostate cancer is associated with progression
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

in Acta Clinica Belgica (1998, January), 53(3), 221-240

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See detailThe 67-kDa laminin receptor originated from a ribosomal protein that acquired a dual function during evolution.
Ardini, E.; Pesole, G.; Tagliabue, E. et al

in Molecular Biology and Evolution (1998), 15(8), 1017-25

The 67-kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that mediates high-affinity interactions between cells and laminin. Overexpression of this protein in tumor cells has been related ... [more ▼]

The 67-kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that mediates high-affinity interactions between cells and laminin. Overexpression of this protein in tumor cells has been related to tumor invasion and metastasis. Thus far, only a full-length gene encoding a 37-kDa precursor protein (37LRP) has been isolated. The finding that the cDNA for the 37LRP is virtually identical to a cDNA encoding the ribosomal protein p40 has suggested that 37LRP is actually a component of the translational machinery, with no laminin-binding activity. On the other hand, a peptide of 20 amino acids deduced from the sequence of 37LR/p40 was shown to exhibit high laminin-binding activity. The evolutionary relationship between 23 sequences of 37LRP/p40 proteins was analyzed. This phylogenetic analysis indicated that all of the protein sequences derive from orthologous genes and that the 37LRP is indeed a ribosomal protein that acquired the novel function of laminin receptor during evolution. The evolutionary analysis of the sequence identified as the laminin-binding site in the human protein suggested that the acquisition of the laminin-binding capability is linked to the palindromic sequence LMWWML, which appeared during evolution concomitantly with laminin. [less ▲]

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See detailTumor angiogenesis : basis for new prognostic factors and new anticancer therapies.
Belotti, D.; Castronovo, Vincenzo ULg

in Clinical and Biological Basis of Lung Cancer Prevention. (1998)

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See detailBone sialoprotein is expressed in both human neuroblastoma tissues and cell lines
Bellahcene, Akeila ULg; Albert, Valérie; Nyabi, Omar et al

in Proceedings of the American Association for Cancer Research (1998), 39

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See detailExpression of bone sialoprotein in human prostate cancer is associated with progression
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

in Proceedings of the American Association for Cancer Research (1998), 39

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