Breast cancer; tumor neovasculature and the effect of tissue inhibitor of metalloproteinases-1 (TIMP-1) on angiogenesis.
Microvessel density has been proposed as a prognostic factor in breast carcinoma. In paired samples of human breast carcinoma and the adjacent non-neoplastic tissue, proliferating microvessels were associated with in situ ductal and lobular carcinomas. In invasive carcinomas, the microvessels were located within the tumor stroma. Recombinant tissue inhibitor of metalloproteinases-1 (rTIMP-1) was produced in a baculovirus system to examine its effect on angiogenesis. When present as a molecule of 29 kDa, rTIMP-1 inhibited matrix metalloproteinase (MMP) activity. However, a 66 kDa aggregate of TIMP-1 did not block MMP activity, although it inhibited in vitro angiogenesis as the 29 kDa form did. Studies have been initiated to characterize the effects of overexpression of TIMP-1 on breast carcinoma cells. Preliminary findings show TIMP-1 mediated changes in morphology and downregulation of MMP activity. These findings suggest that the angiogenesis inhibitory activity of TIMP-1 is unrelated to its antimetalloproteinase activity and that TIMP-1 may affect cellular function in different ways.
Thorgeirsson
U P
UP
Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Yoshiji
H
H
Sinha
C C
CC
Gomez
D E
DE
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology; D002273:Carcinogens / Q000494:pharmacology; D017364:Collagenases / Q000494:pharmacology; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D008970:Molecular Weight; D009389:Neovascularization, Pathologic; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases; D014162:Transfection; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D017077:Culture Media, Conditioned; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D008770:Methylnitrosourea; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9