Specific degradation of subendothelial matrix proteoglycans by brain-metastatic melanoma and brain endothelial cell heparanases

Dario Marchetti

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

One of the many features of the malignant phenotype, in vitro and in vivo, is elevated heparanase production and activity. Using in vitro model systems, we examined the capacity of murine (B16B15b) and human (70W) brain-metastatic melanoma cells to degrade the subendothelial matrix produced by endothelial cell monolayer cultures. B16B15b and 70W melanoma cells solubilized sulfated matrix proteoglycans at levels significantly higher than their parental lines (B16F1, MeWo). Sulfated matrix proteoglycans were rich in heparan sulfate (HSPGs), with minor amounts of chondroitin and dermatan sulfates. When matrix HSPGs were treated with pronase and alkaline borohydride to cleave the core proteins, the resulting glycosaminoglycan chains (GAGs) had an estimated M(r) of ~2.7 x 104 Da, with a minor subpopulation possessing an M(r) of ~4.5 x 104 Da. After their incubation with brain-metastatic melanoma cells, new HS fragments with lower M(r) estimated at -9 x 103 Da were detected. This confirms action in these cells of heparanase, which is capable of cleaving GAGs at specific intrachain sites and releasing fragments of a relatively high M(r). The pattern of HSPG degradation by brain-metastatic melanoma cells differed from that of less metastatic parental cells or cells metastatic to organs other than the brain. Moreover, supraadditive levels of heparanase activity were found when brain endothelial cells were coincubated with brain-metastatic melanoma cells in equicellular amounts. Cooperative interactions between heparanases from tumor and endothelial sources in the invasion process are suggested and their potential mechanisms discussed.

Original languageEnglish (US)
Pages (from-to)334-342
Number of pages9
JournalJournal of Cellular Physiology
Volume172
Issue number3
DOIs
StatePublished - Sep 1997

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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