Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial-endothelial cell interactions.

Journal Article (Journal Article)

The purpose of this study was to investigate the roles of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the formation of capillary structures by human brain microvascular endothelial cells cocultured with SNB19 glioblastoma cells. Unstimulated cocultures did not form capillaries and produce MMP-9 but stimulation with the protein kinase C (PKC) activator 4-phorbol-12-myristate 13-acetate (PMA) produced MMP-9 and capillary networks. Addition of recombinant MMP-9 increased capillary formation. Anti-MMP-9 antibodies, TIMP-1, the synthetic MMPs inhibitor Batimastat (BB-94), and the PKC inhibitor calphostin-C all reduced MMP-9 activity and capillary network formation in these cocultures. Cytochalasin-D in the presence of PMA suppressed MMP-9 expression and capillary formation, but colchicine-B had no such effect. Finally, PMA-induced MMP-9 expression and capillary formation were inhibited by the MEKK-specific inhibitor PD98059. These results suggest that MMP-9 is important in endothelial cell morphogenesis and the formation of capillaries in glial/endothelial cocultures in vitro.

Full Text

Duke Authors

Cited Authors

  • Chandrasekar, N; Jasti, S; Alfred-Yung, WK; Ali-Osman, F; Dinh, DH; Olivero, WC; Gujrati, M; Kyritsis, AP; Nicolson, GL; Rao, JS; Mohanam, S

Published Date

  • 2000

Published In

Volume / Issue

  • 18 / 4

Start / End Page

  • 337 - 342

PubMed ID

  • 11448065

International Standard Serial Number (ISSN)

  • 0262-0898

Digital Object Identifier (DOI)

  • 10.1023/a:1010833730407


  • eng

Conference Location

  • Netherlands