Melanoma Cell Galectin-1 Ligands Functionally Correlate with Malignant Potential

作者：Yazawa Erika M; Geddes Sweeney Jenna E; Cedeno Laurent Filiberto; Walley Kempland C; Barthel Steven R; Opperman Matthew J; Liang Jennifer; Lin Jennifer Y; Schatton Tobias; Laga Alvaro C; Mihm Martin C; Qureshi Abrar A; Widlund Hans R; Murphy George F; Dimitroff Charles J^*

来源：Journal of Investigative Dermatology, 2015, 135(7): 1849-1862.

DOI：10.1038/jid.2015.95

Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can influence melanoma development through dampening antitumor immune responses and promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed on melanoma cells to help control intrinsic malignant features remains poorly understood. Here, we analyzed expression, identity, and function of Gal-1 ligands in melanoma progression. Immunofluorescent analysis of benign and malignant human melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely dysplastic nevi, as well as in primary and metastatic melanomas. Biochemical assessments indicated that melanoma cell adhesion molecule (MCAM) was a major Gal-1 ligand on melanoma cells that was largely dependent on its N-glycans. Other melanoma cell Gal-1 ligand activity conferred by O-glycans was negatively regulated by alpha 2,6 sialyltransferase ST6GalNAc2. In Gal-1-deficient mice, MCAM-silenced (MCAM(KD)) or ST6GalNAc2-overexpressing (ST6(O/E)) melanoma cells exhibited slower growth rates, underscoring a key role for melanoma cell Gal-1 ligands and host Gal-1 in melanoma growth. Further analysis of MCAM(KD) or ST6(O/E) melanoma cells in cell migration assays indicated that Gal-1 ligand-dependent melanoma cell migration was severely inhibited. These findings provide a refined perspective on Gal-1/melanoma cell Gal-1 ligand interactions as contributors to melanoma malignancy.

• 出版日期2015-7