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See detailIncreased Expression of Bone Sialoprotein in Bone Metastases Compared with Visceral Metastases in Human Breast and Prostate Cancers
Waltregny, David ULg; Bellahcene, Akeila ULg; de Leval, Xavier et al

in Journal of Bone and Mineral Research (2000), 15(5), 834-43

The recent demonstration that bone sialoprotein (BSP) is expressed in osteotropic cancers suggests that this bone matrix protein might be implicated in the preferential seed and growth of metastatic cells ... [more ▼]

The recent demonstration that bone sialoprotein (BSP) is expressed in osteotropic cancers suggests that this bone matrix protein might be implicated in the preferential seed and growth of metastatic cells in bone. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. The exact mechanisms by which BSP may favor bone metastases formation are not clearly established yet. Although BSP expression has been detected in breast, prostate, lung, thyroid, and neuroblastoma primary tumors, no information regarding its expression in metastases is available to date. In this study, we have examined BSP expression in 15 bone and 39 visceral metastatic lesions harvested from 8 breast cancer patients and 7 prostate cancer patients who died of disseminated disease. We were able to retrieve the primary lesions from 5 of the 8 breast cancer patients as well as from all 7 prostate cancer patients. All the primary breast tumor patients and 5 of the 7 primary prostate cancer patients expressed a detectable level of BSP. Bone metastases from all 8 breast cancer patients and from 5 out of 7 prostate cancer patients exhibited detectable levels of the protein. Metastatic cells in close contact with bone trabeculae usually were highly positive for BSP. BSP also was detected in secondary lesions developed at visceral sites including liver, thyroid, lung, and adrenal glands. However, BSP expression was significantly lower in visceral metastases than in skeletal ones (Mann-Whitney test, p < 0.05). Our data represent the first demonstration of an increased expression of BSP in bone metastases compared with nonskeletal metastases in human breast and prostate cancers and add weight to the body of evidence attributing a significant role to this protein in the genesis of bone metastases. [less ▲]

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See detailBone Sialoprotein Mediates Human Endothelial Cell Attachment and Migration and Promotes Angiogenesis
Bellahcene, Akeila ULg; Bonjean, K.; Fohr, B. et al

in Circulation Research (2000), 86(8), 885-91

Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in sites of biomineralization. Recently, we demonstrated that BSP is strongly upregulated in osteotropic cancers and particularly those ... [more ▼]

Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in sites of biomineralization. Recently, we demonstrated that BSP is strongly upregulated in osteotropic cancers and particularly those that exhibit microcalcifications. BSP contains an Arg-Gly-Asp (RGD) motif found in other adhesive molecules that interact with cellular integrins. In bone, BSP has been shown to mediate the attachment of osteoblasts and osteoclasts via alpha(v)beta(3) integrin receptors. Ligands for alpha(v)beta(3) integrin are considered to play a central role during angiogenesis. Therefore, we used human umbilical vein endothelial cells (HUVECs) to study the potential role of BSP in angiogenesis. We found that purified eukaryotic recombinant human BSP (rhBSP) is able to promote both adhesion and chemotactic migration of HUVECs in a dose-dependent manner. These interactions involve HUVEC alpha(v)beta(3) integrin receptors and the RGD domain of BSP. Indeed, HUVECs attach to a recombinant BSP fragment containing the RGD domain, whereas this response is not observed with the same fragment in which RGD has been mutated to Lys-Ala-Glu (KAE). A cyclic RGD BSP peptide inhibits both adhesion and migration of HUVECs to rhBSP. Moreover, anti-alpha(v)beta(3) but not anti-alpha(v)beta(5) monoclonal antibodies also prevent BSP-mediated adhesion and migration of HUVECs. We observed that both rhBSP and the RGD BSP recombinant fragment stimulated ongoing angiogenesis on the chorioallantoic chick membrane assay. BSP angiogenic activity was inhibited by anti-alpha(v)beta(3) antibody, and the KAE BSP fragment was inactive. Our findings represent the first report implicating BSP in angiogenesis. BSP could play a critical role in angiogenesis associated with bone formation and with tumor growth and metastatic dissemination. [less ▲]

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See detailCombined Interferon-Gamma and Tumor Necrosis Factor-Alpha Treatment Differentially Affects Adhesion and Migration of Keratinocyte-Derived Cells to Laminin-1
van den Brule, Frédéric A; Clausse, Nathalie; Delvenne, Philippe ULg et al

in Cell Adhesion and Communication (2000), 7(4), 321-9

Interactions with the extracellular matrix constitute basic steps in cervix carcinoma cell invasion. In this study, we examined the adhesion and migration profiles of two human papillomavirus (HPV) DNA ... [more ▼]

Interactions with the extracellular matrix constitute basic steps in cervix carcinoma cell invasion. In this study, we examined the adhesion and migration profiles of two human papillomavirus (HPV) DNA-transfected keratinocyte-derived cell lines, EIL8 and 18-11S3, and of the cervix adenocarcinoma SiHa cell line, towards laminin-1, and the selective effect of a 24-72 h treatment of 1000 U/ml interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), a treatment that significantly decreases cervix carcinoma cell proliferation and progression in nude mice, on these parameters. Compared to normal cervix keratinocytes (CK) and two HPV DNA-transfected keratinocyte cell lines, in basal conditions, the SiHa cell line was characterized by increased attachment (SiHa, 48.74 +/- 4.02 vs. normal keratinocytes, 4.32 +/- 0.40, EIL8, 17.80 +/- 3.03 and 18-11S3, 17.82 +/- 1.48% of attached cells after 30 min) and marked directed chemotactic migration towards laminin-1. Interestingly, treatment of the cells with the cytokines (1000 U/ml IFN-gamma and TNF-alpha) did not modulate the adhesion properties of the cells, but chemotactic migration of SiHa cells to laminin-1 was significantly decreased, while migration towards type I collagen was increased. Similar results were obtained with the Ca Ski cervix carcinoma cell line. Our results emphasize the altered pattern of interactions of cervix carcinoma cells with extracellular matrix components such as laminin-1, compared to normal and pre-neoplastic cells, and contributes to the understanding of the effects of cytokine treatment on cervix carcinoma cells. [less ▲]

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See detailTnp-470, a Potent Angiogenesis Inhibitor, Amplifies Human T Lymphocyte Activation through an Induction of Nuclear Factor-Kappab, Nuclear Factor-at, and Activation Protein-1 Transcription Factors
Locigno, Roberto; Antoine, Nadine ULg; Bours, Vincent ULg et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2000), 80(1), 13-21

TNP-470, an angiogenesis inhibitor derived from fumagillin, is foreseen as a promising anti-cancer drug. Its effectiveness to restrain tumor growth and its lack of major side effects have been ... [more ▼]

TNP-470, an angiogenesis inhibitor derived from fumagillin, is foreseen as a promising anti-cancer drug. Its effectiveness to restrain tumor growth and its lack of major side effects have been demonstrated in several animal models and have led the drug to reach phase III clinical trials. Beside its antiangiogenesis activities, TNP-470 exhibits several effects on the immune system. We had shown previously that TNP-470 stimulated B lymphocyte proliferation through an action on T cells. In this study, we examined the cellular and molecular modifications induced by TNP-470 in normal human T lymphocytes. Transmission electron microscopic examination of PHA/TNP-470-treated T cells revealed significant morphologic modifications when compared with PHA-treated control T cells. TNP-470 induced indeed an important and significant increase of the nuclear size as well as major nuclear chromatin decondensation. This observation indicated that TNP-470 amplified T-cell activation and led us to investigate its effects on the activation of transcription factors involved in T-cell activation. Using electrophoretic mobility shift assays, we have demonstrated that TNP-470 amplifies and extends the DNA-binding activity of nuclear factor-AT, nuclear factor-KB, and activation protein-1 in T cells. Furthermore, the angioinhibin significantly increased the secretion of IL-2 and IL-4. Our data demonstrate that TNP-470 amplifies the activation of T cells. This effect, whose molecular mechanisms remain to be elucidated, has to be taken into account in the assessment of the antitumor effect of the drug. [less ▲]

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See detailDetection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy
Waltregny, David ULg; de Leval, Laurence ULg; Coppens, Luc ULg et al

Conference (2000)

INTRODUCTION & OBJECTIVES: The identification of reliable prognostic indicators for prostate cancer (PC) is a major challenge of today cancer research. The 67-KD laminin receptor (67LR) is a cell surface ... [more ▼]

INTRODUCTION & OBJECTIVES: The identification of reliable prognostic indicators for prostate cancer (PC) is a major challenge of today cancer research. The 67-KD laminin receptor (67LR) is a cell surface associated molecule whose increased expression is associated with the aggressiveness of a variety of human cancers. We recently showed that 67LR detection in PC tissues from radical prostatectomy (RP) specimens was an independent predictor of biochemical relapse in patients with clinically localized PC (JNCI, 89:1224-1227, 1997). In this study, we assessed 67LR detection in diagnostic biopsies as a predictor of biochemical relapse after RP. MATERIAL & METHODS: A total of 151 patients with clinically confined PC underwent RP. PC tissue sections from both biopsy and RP specimens were immunohistochemically analyzed for 67LR expression. The importance of 67LR expression was evaluated according to the intensity and extent of the staining. Preoperative and postoperative clinicopathological parameters, including 67LR expression, were correlated with each other and tested as predictors of biochemical relapse. RESULTS: 67LR was detected in 67.5% and 68.2% of biopsies and RPs, respectively. 67LR detection in RP specimens was an independent predictor of relapse. The level of 67LR expression in the biopsy was significantly associated with the biopsy Gleason score (p<0.05) but failed to predict the pathological stage (p>0.1). Biochemical progression-free estimates for patients whose biopsy did or did not express the protein differed with only borderline statistical significance (p=0.05). Multivariate analysis identified biopsy Gleason score as the only independent preoperative predictor of recurrence. Significant discrepancies in levels of 67LR expression were found between matched biopsy and RP specimens, with exact agreement rates <40% (p<0.05). CONCLUSIONS: 67LR detection in PC biopsies was not a significant preoperative predictor of outcome after RP. Heterogeneity of 67LR expression and biopsy sampling errors most likely represented the main raisons for discordant prognostic results depending on whether 67LR expression was evaluated either in biopsies or in RPs. [less ▲]

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See detailIncreased expression of Galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients
van den Brule, Frédéric; Waltregny, David ULg; Castronovo, Vincenzo ULg

in Proceedings of the American Association for Cancer Research (2000), 41

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See detailDecreased Expression of Galectin-3 in Basal Cell Carcinoma of the Skin
Castronovo, Vincenzo ULg; Liu, F. T.; van den Brule, F. A.

in International Journal of Oncology (1999), 15(1), 67-70

Galectins are beta-galactoside-binding lectins that play multiple roles during tumor progression. Previous work conducted in our laboratory has demonstrated decreased galectin-3 expression in carcinomas ... [more ▼]

Galectins are beta-galactoside-binding lectins that play multiple roles during tumor progression. Previous work conducted in our laboratory has demonstrated decreased galectin-3 expression in carcinomas from colon, breast, ovary and endometrium, compared to the corresponding normal tissues. In this study, we examined the pattern of galectin-3 expression by immunohistochemistry in a group of 10 basal cell carcinomas of the skin. In the surrounding normal skin, galectin-3 immunostaining was found predominantly in the middle epidermis (spine layer) and eccrine sweat glands. Compared to the normal epidermal cells, basal carcinoma cells observed in all 10 samples examined presented with significantly decreased galectin-3 immunostaining. These data further demonstrates that galectin-3 is down-regulated in a variety of human cancers, including basal cell carcinoma. [less ▲]

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See detailThe role of bone sialoprotein in bone metastasis
Bellahcene, Akeila ULg; Waltregny, David ULg; Castronovo, Vincenzo ULg

in Skouteris, G. G.; Nicolson, G. L. (Eds.) Intermolecular Cross-Talk in Tumor Metastasis (1999, May)

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See detailHoxc5 and Hoxc8 Expression Are Selectively Turned on in Human Cervical Cancer Cells Compared to Normal Keratinocytes
Alami, Y.; Castronovo, Vincenzo ULg; Belotti, D. et al

in Biochemical and Biophysical Research Communications (1999), 257(3), 738-45

A growing number of data have sustained the involvement of homeobox genes expression deregulation in cancer. In this study, we have performed an exhaustive survey of the expression of the 39 class I HOX ... [more ▼]

A growing number of data have sustained the involvement of homeobox genes expression deregulation in cancer. In this study, we have performed an exhaustive survey of the expression of the 39 class I HOX genes expressed in normal and malignant human cervix keratinocytes. Using RT-PCR, we observed that the vast majority (34/39) of HOX genes are expressed in normal keratinocytes. Only HOXA2, HOXA7, HOXC5, HOXC8 and HOXD12 were found to be silent. Interestingly, this pattern is conserved in the transformed keratinocytes (SiHa cells) except for the appearance of HOXC5 and HOXC8 mRNA. The HOXC5 and HOXC8 expression was also observed in two other transformed keratinocytes cell lines of independent origins, Eil-8 and 18-11S3, and confirmed by in situ hybridization. Our data add weight to the body of evidence attributing to a specific adult tissue a particular combination of expressed HOX genes and suggest that HOXC5 and/or HOXC8 could be involved in the process leading to the transformation of cervical keratinocytes. [less ▲]

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See detailCell surface immunophenotype and gelatinase activity of the human breast carcinoma cell line (MCF-7/6) with functionally defective E-cadherin.
Hlavcak, P.; Sedlakova, O.; Sedlak, J. et al

in Neoplasma (1999), 46(1), 12-6

Expression of differentiation and adhesion cell surface antigens (LewisX - CD15, CD44, syndecan 1 - CD138 and basigin/EMMPRIN - CD147) were determined on the cell surface of human breast carcinoma MCF7 ... [more ▼]

Expression of differentiation and adhesion cell surface antigens (LewisX - CD15, CD44, syndecan 1 - CD138 and basigin/EMMPRIN - CD147) were determined on the cell surface of human breast carcinoma MCF7 cells in vitro with the aid of flow cytometry and compared with that of MCF-7/6 cells, with functionally defective E-cadherin system and increased biological aggressiveness. The major cell surface alterations in MCF-7/6 cells compared with the parental MCF-7 cell line were a markedly increased CD15 (LewisX) and CD44 antigen cell surface expression on MCF-7/6 cells. There were no major differences between parental MCF-7 and MCF-7/6 cells in cell surface syndecan 1, basigin/EMMPRIN, E-cadherin and high affinity non-integrin laminin receptor expression. The constitutive cell surface gelatinase A and B activities were absent on MCF-7 and faint in MCF-7/6 cells. Both phorbol ester TPA and tumor necrosis factor TNF-alpha induced a marked up-regulation of gelatinase B only in MCF-7/6 cells. No marked differences in penetration of MCF-7 vs. MCF-7/6 cells into collagen/fibroblast matrix in vitro were observed. The increased expression of CD15 (LewisX), CD44 antigen and TNF-alpha-inducible gelatinase B on MCF-7/6 cells may represent auxiliary factors contributing to the increased biological aggressiveness of MCF-7/6 cells. [less ▲]

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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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