Differential expression of proteoglycans on the surface of human melanoma cells characterized by altered experimental metastatic potential

Abstract

Heparan sulphate (HS) and chondroitin sulphate (CS) proteoglycans (PGs) frequently have opposite biologic functions in cell-matrix adhesion as well as in the regulation of cell proliferation. Data revealed that sulphated glycosaminoglycans (sGAGs) (sugar chains of PGs) are differently expressed in tumor cells characterized by different metastatic potential; the more metastatic cells contain a higher HS/CS ratio. As the proliferative capacity of tumor cells is also frequently altered in parallel with their metastatic potential, it was not clear whether observed PG alterations reflect changes in cell proliferation or metastatic potential. The cell-associated PG expression and sGAG biosynthesis was studied in tumor cells of human melanoma lines characterized by different experimental metastatic potential to the mouse liver but similar in vitro/in vivo proliferation rates. Using antibodies against PGs we found different expression of PG epitopes in melanoma lines, except from the melanoma antigen. Unlike the low CSPG (melCSPG) metastatic melanoma cells, the cell line with high metastatic capacity contained a higher proportion of positive cells for surface-HSPG without the coexpression of certain cartilage-type CSPG epitopes (recognized by MAb HSFPG 529) as well as by an increased pericellular HS/CS ratio due to intracellular accumulation/retention of CS. Immunocytochemistry of adherent cells revealed HSPGs at substrate-attached membrane areas only in cases of highly metastatic melanoma cells. These data further support our view that the absolute or relative dominance of HSPGs over CSPGs at the cell surface of metastatic tumor cells can be considered a marker of a more metastatic phenotype.