A novel function for galectin-7: promoting tumorigenesis by up-regulating MMP-9 gene expression.
Metastasis is a multistep process by which cancer cells, after acquiring several capabilities, spread to distinct sites in the body. It is the major cause of death in individuals suffering from cancer. We have recently identified galectin-7 as a new gene associated with the progression of T cell lymphoma toward a metastatic phenotype, suggesting a possible causal relationship. The present study was designed to investigate the role of galectin-7 in lymphoma. We found that the development of thymic lymphoma was accelerated when induced by lymphoma cells overexpressing galectin-7. Moreover, transfection of an expression vector containing the galectin-7 gene in low metastatic lymphoma cells increased their metastatic behavior and confers these cells with the new ability to overcome the resistance of intercellular adhesion molecule-1-deficient mice to lymphoma dissemination. Finally, we provide data suggesting that galectin-7 modulates the aggressive behavior of lymphoma cells by controlling the expression of metastatic genes, such as MMP-9. This hypothesis is based on the following evidence: (a) galectin-7 transfectants have higher levels of MMP-9 expression, (b) addition of beta-lactose completely inhibits expression of MMP-9 by galectin-7 transfectants, and (c) recombinant forms of galectin-7 induces the expression of MMP-9 in both mouse and human lymphoma cells. Our results have uncovered the existence of a previously undescribed activity, the promotion of cancer cell malignancy, to galectin-7.
Demers
Mélanie
M
INRS-Institut Armand-Frappier, University of Québec, Laval, Québec, Canada.
Magnaldo
Thierry
T
St-Pierre
Yves
Y
D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D037161:Galectins / Q000235:genetics / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D014162:Transfection; D015854:Up-Regulation
D037161:Galectins; C490487:Lgals7 protein, mouse; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9