Modulation of endothelial cell morphogenesis in vitro by MMP-9 during glial-endothelial cell interactions.
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.
Chandrasekar
N
N
Department of Biomedical and Therapeutic Sciences, UIC College of Medicine at Peoria, Illinois 61656, USA.
Jasti
S
S
Alfred-Yung
W K
WK
Ali-Osman
F
F
Dinh
D H
DH
Olivero
W C
WC
Gujrati
M
M
Kyritsis
A P
AP
Nicolson
G L
GL
Rao
J S
JS
Mohanam
S
S
D001921:Brain / Q000098:blood supply*; D002196:Capillaries; D002273:Carcinogens / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D009457:Neuroglia / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000502:physiology*
D002273:Carcinogens; D019715:Tissue Inhibitor of Metalloproteinase-1; D011493:Protein Kinase C; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate