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: Véronique Mathieu, Elisabeth Martin de Lassalle, Jaan Toelen, Thomas Mohr, Akeila Bellahcène, Gwendoline Van Goietsenoven, Tina Verschuere, Caroline Bouzin, Zeger Debyser, Steven De Vleeschouwer, Stefaan Van Gool, Françoise Poirier, Vincent Castronovo, Robert Kiss, Olivier Feron
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 132 Issue 9 Pg. 2245-54 (Sep 2012) ISSN: 1523-1747 [Electronic] United States
• PMID: 22622427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Galectin 1
• Proto-Oncogene Proteins p21(ras)

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Endothelial Cells (metabolism, pathology)
• Galectin 1 (metabolism)
• Gene Knockdown Techniques
• Lung Neoplasms (genetics, metabolism, secondary)
• Melanoma, Experimental (genetics, metabolism, secondary)
• Mice
• Neovascularization, Pathologic (genetics, metabolism, pathology)
• Proto-Oncogene Proteins p21(ras) (metabolism)
• Skin Neoplasms (genetics, metabolism, pathology)