Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial-endothelial cell interactions* |
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Authors: | Nirmala Chandrasekar Sushma Jasti WK Alfred-Yung Francis Ali-Osman Dzung H Dinh William C Olivero Meena Gujrati Athanassios P Kyritsis Garth L Nicolson Jasti S Rao Sanjeeva Mohanam |
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Institution: | (1) Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, USA;(2) Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA;(3) Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA;(4) Neurosurgery, UIC College of Medicine at Peoria, Peoria, Illinois, USA;(5) Pathology, UIC College of Medicine at Peoria, Peoria, Illinois, USA;(6) The Institute for Molecular Medicine, Huntington Beach, California, USA;(7) Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences and Department Neurosurgery, UIC College of Medicine at Peoria, Peoria, Illinois, USA |
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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.
This revised version was published online in July 2006 with corrections to the Cover Date. |
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Keywords: | angiogenesis extracellular matrix glioblastoma MMP-9 TIMPs |
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