期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 135, 期 7, 页码 1849-1862出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2015.95
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资金
- NIH [1S10OD010612]
- NIH/NCI [R01CA173610, RO1CA158467]
- NIH Kirschstein-NRSA Post-doctoral Fellowship award [F32CA144219]
- NIH Pre-doctoral Fellowship Award [F31CA171520]
- Dermatology Foundation Research grant
- American Cancer Society New England Division Postdoctoral Fellowship [PF-10-227-01-CSM]
- BWH Department of Dermatology Developmental SPORE Grant [P50CA093683]
- Research Career Development Award, Dermatology Foundation
- Innovative Research Grant, Melanoma International Foundation
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.
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