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Expression of the NG2 proteoglycan enhances the growth and metastatic properties of melanoma cells
Author(s) -
Burg Michael A.,
Grako Kathryn A.,
Stallcup William B.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199811)177:2<299::aid-jcp12>3.0.co;2-5
Subject(s) - cd44 , melanoma , biology , cancer research , fibronectin , proteoglycan , cell culture , integrin , transfection , cell adhesion molecule , cell growth , cell adhesion , metastasis , microbiology and biotechnology , cell , extracellular matrix , cancer , biochemistry , genetics
The human homologue of NG2, the human melanoma proteoglycan (HMP), is expressed on most human melanomas. To investigate the role of this proteoglycan in melanoma progression, we have attempted to identify functionally important molecular ligands for NG2. Immunohistochemical analysis of cell lines that endogenously express NG2/HMP suggests that NG2/HMP associates with CD44 and α 4 β 1 integrin, two molecules previously implicated in melanoma progression. Transfection of rat NG2 into the NG2‐negative B16 mouse melanoma cell line also resulted in a highly colocalized pattern of expression between the transfected rat NG2 and the endogenously expressed mouse CD44 and α 4 β 1 integrin molecules. In functional assays, expression of NG2 decreased the adhesion of B16 melanoma cells to CD44 monoclonal antibodies, hyaluronic acid, the C‐terminal 40‐kDa fibronectin fragment, and the CS1 fibronectin peptide, suggesting that NG2 may negatively modulate CD44‐ and α 4 β 1 ‐mediated binding events. Expression of NG2 increased the proliferation of melanoma cells in culture and increased tumorigenicity in vivo. Moreover, NG2 expression led to increased lung metastasis of B16F1 and B16F10 melanoma cells in experimental metastasis studies. Together, these studies demonstrate that NG2 is capable of modulating the adhesion, proliferation, and metastatic potential of melanoma cells. J. Cell. Physiol. 177:299–312, 1998. © 1998 Wiley‐Liss, Inc.