Alterations in endothelial cell proteinase and inhibitor polarized secretion following treatment with interleukin-1, phorbol ester, and human melanoma cell conditioned medium.
Polarized secretion of matrix metalloproteinases and plasminogen activators by monkey aortic endothelial cells was studied in vitro, using transwell inserts. The endothelial cells constitutively expressed matrix metalloproteinase-2, tissue inhibitors of metalloproteinases 1 and 2, urokinase, and tissue plasminogen activator, all with basal preference. Matrix metalloproteinase-9 activity was induced by phorbol 12-myristate 13-acetate (apical), interleukin-1 alpha (basal), and by conditioned medium from DX3 human melanoma cells (basal). The DX3 melanoma conditioned medium also stimulated basal secretion of matrix metalloproteinase-2, urokinase, tissue plasminogen activator, and tissue inhibitors of metalloproteinases. The rise in proteolytic activity in the basal direction was reflected by increased capacity to degrade subendothelial basement membrane type IV collagen, shown immunohistologically, using monkey kidney tissue sections and basement membrane deposited by endothelial cells into the transwell membrane. Thus, IL-1 alpha and DX3 melanoma conditioned medium can stimulate endothelial cells in vitro to concentrate secretion of proteinases spatially onto the underlying basement membrane. We suggest that the stimulation of endothelial cell proteinase activity by tumor cells may facilitate tumor cell extravasation.
Cottam
D W
DW
Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Corbitt
R H
RH
Gomez
D E
DE
Rees
R C
RC
Thorgeirsson
U P
UP
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D017077:Culture Media, Conditioned; D007375:Interleukin-1; D011994:Recombinant Proteins; D003094:Collagen; D010959:Tissue Plasminogen Activator; D008666:Metalloendopeptidases; D013755:Tetradecanoylphorbol Acetate