Lignées de carcinome prostatique et apoptose: état de la question

in Revue Médicale de Liège (2004), 59(12), 704-10

Prostate cancer is a major pathology in industrialized countries. Tumor growth usually results from increased cell proliferation, conjugated with an inhibition of programmed cell death (apoptosis). In ... [more ▼]

Prostate cancer is a major pathology in industrialized countries. Tumor growth usually results from increased cell proliferation, conjugated with an inhibition of programmed cell death (apoptosis). In this paper, after a short description of the apoptotic mechanisms and their methods of investigation, we review the present knowledge of the implication of different molecular actors in the regulation of apoptosis in prostate cancer cells. This review notably summarizes the present knowledge of the (de)regulation of the effects of androgens, p53, Bcl-2, Bcl-xL, Bax, Akt, PTEN, Par-4, clusterine, caspases and NF-kappaB in prostate adenocarcinoma cell lines and provides an appraisal of their therapeutic potential. A better knowledge of the apoptotic pathways in these cells could indeed allow the development of new selective and effective anti-cancer strategies. [less ▲]

Expression of Galectins in Cancer: A Critical Review

in Glycoconjugate Journal (2004), 19(7-9), 537-42

A large body of literature has examined and described galectin expression in cancer. Discrepancies have been observed in the reported data, which hampered clear understanding of the expression profiles ... [more ▼]

A large body of literature has examined and described galectin expression in cancer. Discrepancies have been observed in the reported data, which hampered clear understanding of the expression profiles. This relates to the use of different types of methods that evaluate either global or specific gene expression in heterogeneous cancer tissue samples, type of antibodies used in immunohistochemistry and procedures of comparison of gene expression. In this manuscript, we review the main data concerning expression of galectins in human cancer. Only galectin-1 and galectin-3, the most abundant and examined galectins, will be examined here. [less ▲]

Increased Expression of Galectin-1 in Carcinoma-Associated Stroma Predicts Poor Outcome in Prostate Carcinoma Patients

in Journal of Pathology (The) (2001), 193(1), 80-7

Galectin-1, a member of the beta-galactoside-binding galectin family, is a pleiotropic dimeric protein participating in a variety of normal and pathological processes, including cancer progression ... [more ▼]

Galectin-1, a member of the beta-galactoside-binding galectin family, is a pleiotropic dimeric protein participating in a variety of normal and pathological processes, including cancer progression. Modulation of the interactions with the basement membrane glycoprotein laminin and induction of apoptosis in activated T lymphocytes are well-known functions of this galectin. In this study, the expression of galectin-1 was examined in 148 human primary prostate carcinoma samples. Immunohistochemical staining of paraffin sections of prostate tissues revealed that galectin-1 was not detected in normal, PIN (prostatic intraepithelial neoplasia) or carcinoma cells, but accumulated in the stroma and associated fibroblasts. Galectin-1 expression was significantly increased in the tumour-associated stroma compared with the non-neoplastic gland-associated stroma in 21.3% of the cases (Mantel-Haenszel test, p=0.001; Wilcoxon signed rank test, p<0.0001). Increased galectin-1 expression in the cancer-associated stroma compared to the normal gland-associated stroma (p=0.03) was identified by multivariate analysis as a strong independent predictor of prostate-specific antigen (PSA) recurrence, just after the pathological stage (p<0.0001). The association between accumulation of galectin-1 in the stroma of the malignant tissue and aggressiveness of the tumour adds weight to the body of evidence that identifies a role for galectin-1 in the acquisition of the invasive phenotype. In addition to modulating cancer cell interactions with laminin, galectin-1 accumulated around the cancer cells may act as an immunological shield by inducing activated T-cell apoptosis. This exciting hypothesis warrants further investigation. [less ▲]

Increased expression of Galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients

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

Galectin-1 Expression in Prostate Tumor-Associated Capillary Endothelial Cells Is Increased by Prostate Carcinoma Cells and Modulates Heterotypic Cell-Cell Adhesion

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 ▲]

Differential expression of galectin-1 and galectin-3 during first trimester human embryogenesis.

in Developmental Dynamics : An Official Publication of the American Association of Anatomists (1997), 209(4), 399-405

Development of complex organisms requires specific temporospatial differentiation and expression of the correct phenotype through activation of a variety of genes. Galectins are mammalian lectins able to ... [more ▼]

Development of complex organisms requires specific temporospatial differentiation and expression of the correct phenotype through activation of a variety of genes. Galectins are mammalian lectins able to interact with various extracellular matrix glycoconjugates and have been implicated in several biological events including cell attachment, differentiation, apoptosis, embryogenesis, and cancer invasion and metastasis. In this study, we have examined the expression of galectin-1 and galectin-3 during human first trimester embryogenesis using immunohistochemistry and Western blotting. Variable amounts of galectin-1 and galectin-3 were detected in all tissue protein extracts. Galectin-1 expression was demonstrated in the connective tissue and derived tissues such as smooth and striated muscle cells, and in some epithelia, such as in the basal layers of the skin after 14 weeks and in the epithelial cells of the gonads. Galectin-3 was detected mainly in epithelia, such as the skin, epithelial lining of the digestive and respiratory tract, and urothelium and excretory tubes of the kidney, but also in the myocardial cells, in the peripheral and preossifying hypertrophic chondrocytes, and in the notochord and in the liver. Our study constitutes the first demonstration of galectin-1 and galectin-3 during human embryogenesis. The differential expression of these two lectins suggests that they could participate in the complex processes of tissue differentiation. [less ▲]

Decreased expression of galectin-3 is associated with progression of human breast cancer.

in Journal of Pathology (The) (1996), 179(1), 43-48

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of ... [more ▼]

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of galectin-3 during the interactions between cells and laminin is not yet known, it has recently been observed that its expression is down-regulated at both the protein and the mRNA level in colon cancer tissues in correlation with progression of the disease. This study investigated the possibility that breast cancer cells might also exhibit decreased galectin-3 expression in association with their aggressiveness. The expression of galectin-3 was examined by immunoperoxidase staining, using a polyclonal antibody raised against recombinant galectin-3, in a collection of 98 human breast lesions including 12 fibroadenomas, 15 fibrocystic disease lesions, 22 in situ carcinomas, and 49 infiltrating ductal carcinomas, 19 of which had positive axillary lymph nodes. Normal breast tissue adjacent to the lesions was present in 59 biopsies. Normal breast tissue expressed high levels (3+) of galectin-3. High expression (2+ to 3+) was also found in most benign lesions examined. The expression of galectin-3 was significantly decreased in in situ carcinoma and this down-regulation was more pronounced in invasive ductal carcinoma, particularly when associated with infiltration of axillary lymph nodes. These data constitute the first observation that galectin-3 is down-regulated in breast cancer and suggest the decreased expression of this galactoside-binding lectin is associated with the acquisition of the invasive and metastatic phenotype. [less ▲]

Adhesion of cancer cells to laminin: a critical event of tumor invasion and metastasis

in Vèmes Journées Liégeoises de Gynécologie - Obstétrique (1993)