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.