title: Galectin-1 in melanoma biology and related neo-angiogenesis processes.
abstract: 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.
authors.affiliation: Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Brussels, Belgium. vemathie@ulb.ac.be
authors.forename: Véronique
authors.initials: V
authors.lastname: Mathieu
authors.forename: Elisabeth Martin
authors.initials: EM
authors.lastname: de Lassalle
authors.forename: Jaan
authors.initials: J
authors.lastname: Toelen
authors.forename: Thomas
authors.initials: T
authors.lastname: Mohr
authors.forename: Akeila
authors.initials: A
authors.lastname: Bellahcène
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Van Goietsenoven
authors.forename: Tina
authors.initials: T
authors.lastname: Verschuere
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Steven
authors.initials: S
authors.lastname: De Vleeschouwer
authors.forename: Stefaan
authors.initials: S
authors.lastname: Van Gool
authors.forename: Françoise
authors.initials: F
authors.lastname: Poirier
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D037483:Galectin 1 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D037483:Galectin 1; D016283:Proto-Oncogene Proteins p21(ras)