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

N. Chandrasekar, S. Jasti, W. K. Alfred-Yung, F. Ali-Osman, D. H. Dinh, W. C. Olivero, M. Gujrati, A. P. Kyritsis, G. L. Nicolson, J. S. Rao, S. Mohanam

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)337-342
Number of pages6
JournalClinical and Experimental Metastasis
Volume18
Issue number4
DOIs
StatePublished - Jan 1 2000

Keywords

  • Angiogenesis
  • Extracellular matrix
  • Glioblastoma
  • MMP-9
  • TIMPs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chandrasekar, N., Jasti, S., Alfred-Yung, W. K., Ali-Osman, F., Dinh, D. H., Olivero, W. C., Gujrati, M., Kyritsis, A. P., Nicolson, G. L., Rao, J. S., & Mohanam, S. (2000). Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial-endothelial cell interactions. Clinical and Experimental Metastasis, 18(4), 337-342. https://doi.org/10.1023/A:1010833730407