title: Melanoma Cell Galectin-1 Ligands Functionally Correlate with Malignant Potential.
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.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Erika M
authors.initials: EM
authors.lastname: Yazawa
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jenna E
authors.initials: JE
authors.lastname: Geddes-Sweeney
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Filiberto
authors.initials: F
authors.lastname: Cedeno-Laurent
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Kempland C
authors.initials: KC
authors.lastname: Walley
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Barthel
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Opperman
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Lin
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schatton
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Alvaro C
authors.initials: AC
authors.lastname: Laga
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.affiliation: Department of Dermatology, The Warren Albert Medical School, Brown University, Providence, Rhode Island, USA.
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Widlund
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA. Electronic address: cdimitroff@rics.bwh.harvard.edu.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Dimitroff
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D051929:CD146 Antigen / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D037483:Galectin 1 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D051929:CD146 Antigen; D037483:Galectin 1; D008024:Ligands; C497902:MCAM protein, human