Selective degradation of basement membrane macromolecules by metastatic melanoma cells.
The extracellular matrix deposited in culture by the mouse endodermal cell line (PF HR9) was used as an experimental model to study the interactions between basement membranes and several tumorigenic and nontumorigenic cell lines, including the metastatic B16 melanoma cell sublines. Analysis by biochemical and immunologic methods indicated that the isolated HR9 extracellular matrix was composed of laminin, type IV collagen, entactin, and heparan sulfate proteoglycans--all basement membrane-specific macromolecules. Ultrastructurally, the extracellular matrix elaborated by the HR9 cells appears as a meshwork of finely fibrillar material. B16 melanoma cells were found to adhere rapidly to the isolated HR9 matrix, but significant penetration into the structure was not observed. However, the melanoma cells did induce an extensive solubilization of 35S-sulfate-labeled heparan sulfate to fragments that were approximately one-third the size of the intact heparan sulfate chains. Only the B16 melanoma sublines exhibited this unique pattern of proteoglycan degradation, which suggests that they possess an endoglycosidase specific for heparan sulfate chains. B16 melanoma cells seeded onto HR9 matrices labeled with [1H]leucine or [3H]proline caused no detectable increase in matrix protein solubilization compared to controls. The results indicate that the metastatic tumor cells degrade the proteoglycans in the HR9 matrix more readily than the other matrix proteins.
D001485:Basement Membrane / Q000378:metabolism*; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000302:isolation & purification; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D006023:Glycoproteins / Q000032:analysis; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000302:isolation & purification; D008545:Melanoma / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008854:Microscopy, Electron; D009362:Neoplasm Metastasis; D011347:Procollagen / Q000032:analysis; D011509:Proteoglycans / Q000302:isolation & purification / Q000378:metabolism
D011508:Chondroitin Sulfate Proteoglycans; D006023:Glycoproteins; D007797:Laminin; D008562:Membrane Glycoproteins; D011347:Procollagen; D011509:Proteoglycans; C029967:nidogen; D006026:Glycoside Hydrolases