Galectin-1 in melanoma biology and related neo-angiogenesis processes.
(2012) The Journal of Investigative Dermatology — Vol. 132, n° 9, p. 2245-2254 (2012)
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- Aggressiveness of advanced melanomas relates in part to their marked propensity to develop neoangiogenesis and metastases. Among its numerous pro-cancer roles, galectin (gal)-1 expressed and/or secreted by both cancer and endothelial cells stimulates proliferation and angiogenesis. This study first shows that gal-1 is more highly expressed at both mRNA and protein levels than its congeners in melanomas and particularly in advanced lesions. The roles of gal-1 were further investigated in vivo in the highly proliferating and vascularized pseudometastatic B16F10 mouse melanoma model using stable knockdown B16F10 cells and wild-type versus gal-1 knockout mice, and then in vitro in B16F10 tumoral and lung microvascular cells. Gal-1 depletion in the B16F10 tumor cells but not in the tumor-bearing mice significantly increased melanoma-bearing mice survival. Tumor-derived gal-1 thus seems to have more critical roles than the host-derived one. In fact, gal-1 displays distinct effects on the H-Ras-dependent p53/p21 pathways: in primary lung microvessel endothelial cells, gal-1 seems to be involved in the maintenance of senescent status through the induction of both p53 and p21 while it stimulates B16F10 cancer cell proliferation through a p53/p21 decrease. Altogether, these data point to gal-1 as a potential target to combat melanomas.
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Mathieu, V., de Lassalle, E. M., Toelen, J., Mohr, T., Bellahcène, A., Van Goietsenoven, G., Verschuere, T., Bouzin, C., Debyser, Z., De Vleeschouwer, S., Van Gool, S., Poirier, F., Castronovo, V., Kiss, R., & Feron, O. (2012). Galectin-1 in melanoma biology and related neo-angiogenesis processes. The Journal of Investigative Dermatology, 132(9), 2245-2254. https://doi.org/10.1038/jid.2012.142 (Original work published 2012)