Solubilization and degradation of subendothelial matrix glycoproteins and proteoglycans by metastatic tumor cells

Kramer, R.H.; Vogel, K.G.; Nicolson, G.L.

Journal of Biological Chemistry 257(5): 2678-2686


ISSN/ISBN: 0021-9258
PMID: 7061442
Accession: 006435667

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Successful blood-borne tumor metastasis depends on the abilities of the arrested tumor cell to invade the endothelium and associated basement membrane, permitting subsequent tumor cell migration to an extravascular compartment. In an in vitro model system the capacity of metastatic murine B16 melanoma cells to invade, solubilize and degrade the subendothelial matrix produced by vascular endothelial cell monolayer cultures was studied. Mouse B16 melanoma cells invaded subendothelial matrix with the concurrent solubilization of matrix polypeptides and sulfated proteoglycans in a process which required tumor cell-matrix contact but was not dependent on serum plasmin production. Fibronectin, a major polypeptide constituent of the matrix, was solubilized from matrix by melanoma cells and appeared in the supernatant medium in a partially degraded form. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions revealed a decrease in the MW of the solubilized fibronectin from MW .apprx. 230,000 to .apprx. 225,000. Sulfated proteoglycans in the matrix were rich in heparan sulfate with minor amounts of chondroitin 6-sulfate and chondroitin 4-sulfate. The relative molecular mass of sulfated proteoglycans as determined on Sepharose columns in the presence of 4 M guanidine-HCl was .apprx. 1 .times. 106. After incubation of the matrix with tumor cells, a new low MW heparan sulfate glycosaminoglycan chains produced from matrix proteoglycans by treatment with alkaline borohydride were approximately 3 times larger than this fragment suggested that the tumor cells elaborated a glycosidase capable of cleaving specifically glycosaminoglycans and releasing heparan sulfate-rich fragments. The pattern of degradation of matrix fibronectin and sulfated proteoglycans appeared to be unique to the tumor cells since no such products were detected in the medium from endothelial cells.