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PMID: 1730766 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion.

The Journal of cell biology ·Vol. 116 ·No. 2 ·1992-01-00 ·Pages 521-31

Faassen AE, Schrager JA, Klein DJ, Oegema TR, Couchman JR, McCarthy JB

Abstract

The metastatic spread of tumor cells occurs through a complex series of events, one of which involves the adhesion of tumor cells to extracellular matrix (ECM) components. Multiple interactions between cell surface receptors of an adherent tumor cell and the surrounding ECM contribute to cell motility and invasion. The current studies evaluate the role of a cell surface chondroitin sulfate proteoglycan (CSPG) in the adhesion, motility, and invasive behavior of a highly metastatic mouse melanoma cell line (K1735 M4) on type I collagen matrices. By blocking mouse melanoma cell production of CSPG with p-nitrophenyl beta-D-xylopyranoside (beta-D-xyloside), a compound that uncouples chondroitin sulfate from CSPG core protein synthesis, we observed a corresponding decrease in melanoma cell motility on type I collagen and invasive behavior into type I collagen gels. Melanoma cell motility on type I collagen could also be inhibited by removing cell surface chondroitin sulfate with chondroitinase. In contrast, type I collagen-mediated melanoma cell adhesion and spreading were not affected by either beta-D-xyloside or chondroitinase treatments. These results suggest that mouse melanoma CSPG is not a primary cell adhesion receptor, but may play a role in melanoma cell motility and invasion at the level of cellular translocation. Furthermore, purified mouse melanoma cell surface CSPG was shown, by affinity chromatography and in solid phase binding assays, to bind to type I collagen and this interaction was shown to be mediated, at least in part, by chondroitin sulfate. Additionally we have determined that mouse melanoma CSPG is composed of a 110-kD core protein that is recognized by anti-CD44 antibodies on Western blots. Collectively, our data suggests that interactions between a cell surface CD44-related CSPG and type I collagen in the ECM may play an important role in mouse melanoma cell motility and invasion, and that the chondroitin sulfate portion of the proteoglycan seems to be a critical component in mediating this effect.

MeSH Terms
Animals Antigens, Neoplasm/physiology Antigens, Surface/physiology Cell Adhesion Cell Membrane/metabolism Cell Movement/drug effects Chondroitin Lyases/pharmacology Chondroitin Sulfate Proteoglycans/metabolism Collagen/metabolism Fibronectins/metabolism Glycosides/pharmacology In Vitro Techniques Melanoma, Experimental/pathology Mice Neoplasm Metastasis Receptors, Lymphocyte Homing/physiology
Chemicals
Antigens, Neoplasm Antigens, Surface Chondroitin Sulfate Proteoglycans Fibronectins Glycosides Receptors, Lymphocyte Homing xylosides Collagen Chondroitin Lyases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Faassen A E
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
Schrager J A
Klein D J
Oegema T R
Couchman J R
McCarthy J B
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
1992-01-00
Pages
521-31
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2289300
Subset
IM
Grants
NIAMS NIH HHS · AR32372 · United States
NCI NIH HHS · CA43924 · United States
NIDDK NIH HHS · R01DK39786-05 · United States
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