Heparan sulfate endoglycosidase and metastatic potential in murine fibrosarcoma and melanoma.
Several fibroblast and melanoma cell lines were studied with respect to their ability to degrade heparan sulfate (HS). The optimum pH for HS degradation by HS endoglycosidase (heparanase) for all cell lines is about 5.6, but the activity of the enzyme is still present at physiological pH. The gel permeation analysis of degradation products revealed that heparanase cuts HS in fragments about one-seventh of their original size. Since the optimum pH of HS endoglycosidase activity and the terminal molecular weight of degraded HS are the same in both cell lines, it is likely that fibrosarcoma and melanoma heparanases are identical enzymes. Cell extracts and intact cells of metastatic sublines degrade HS faster than do their nonmetastatic counterparts. The degradative activity of intact cells parallels those of cell extracts, but at a much lower level; moreover, conditioned media do not appreciably degrade HS, suggesting that heparanase is scarcely released into the medium; thus, considering the differences in degradative activity between cell extracts and intact cells or conditioned medium and the occurrence of cell lysis in a tumor in vivo, we suggest that the measure of degradative activity of intact cells in vitro is not indicative of a relationship to metastasis. The total cellular content of lytic enzymes could represent the real metastatic potential of proliferating cells, but it is also necessary to find an in vitro model better representing the behavior of neoplastic cells in vivo.
D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology; D005966:Glucuronidase; D006026:Glycoside Hydrolases / Q000032:analysis*; D006497:Heparan Sulfate / Q000032:analysis / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008970:Molecular Weight; D009362:Neoplasm Metastasis; D000099175:Heparanase
D005966:Glucuronidase; D006026:Glycoside Hydrolases; D006497:Heparan Sulfate; D000099175:Heparanase