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J Invest Dermatol. 2015 Jul;135(7):1849-1862. doi: 10.1038/jid.2015.95. Epub 2015 Mar 10.

Melanoma Cell Galectin-1 Ligands Functionally Correlate with Malignant Potential.

Author information

1
Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
2
Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
3
Harvard Medical School, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
4
Department of Dermatology, The Warren Albert Medical School, Brown University, Providence, Rhode Island, USA.
5
Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA. Electronic address: cdimitroff@rics.bwh.harvard.edu.

Abstract

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 α2,6 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.

PMID:
25756799
PMCID:
PMC4466041
DOI:
10.1038/jid.2015.95
[Indexed for MEDLINE]
Free PMC Article

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