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Mammary carcinoma cells over‐expressing tissue inhibitor of metalloproteinases‐1show vascular endothelial growth factor expression
Author(s) -
Yoshiji Hitoshi,
Harris Steven R.,
Raso Erzsebet,
Gomez Daniel E.,
Lindsay Carol K.,
Shibuya Masabumi,
Sinha Constance C.,
Thorgeirsson Unnur P.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980105)75:1<81::aid-ijc13>3.0.co;2-g
Subject(s) - matrix metalloproteinase , vascular endothelial growth factor , carcinoma , cancer research , vascular endothelial growth factor c , vegf receptors , vascular endothelial growth factor a , mammary carcinoma , biology , pathology , medicine
The tissue inhibitor of metalloproteinases‐1 (TIMP‐1) has at least 2 independent functions, i.e., regulation of matrix metalloproteinases and erythroid‐potentiating activity. We investigated the effects of TIMP‐1 over‐expression on tumor growth, using cloned lines derived from a TIMP ‐1‐transfected rat breast carcinoma cell line. The in vitro growth rate of the TIMP ‐1‐transfected clones was indistinguishable from that of the control. In contrast, the highest TIMP‐1‐producing clone (159.0 ng/ml), designated as T‐H, formed 4.6‐fold larger s.c. tumors than did the control after 14 days. Tumors derived from an intermediate TIMP‐1‐producing clone (45.4 ng/ml), designated as T‐M, were 1.9‐fold larger than the control. TIMP‐1 over‐expression was associated with increased vascular endothelial growth factor (VEGF) expression, vascularization and proliferative activity of the s.c. tumors. Similar to the rat breast carcinoma cells, transfection of TIMP‐1 cDNA into the human breast carcinoma cell line MCF‐7 resulted in up‐regulation of VEGF, with a linear relationship between TIMP‐1 and VEGF production in 9 cell clones examined. There was, however, no change in VEGF expression when the rat and human breast carcinoma cell lines were exposed to exogenous recombinant TIMP‐1. Our findings suggest that over‐expression of TIMP‐1 confers growth advantage on breast carcinoma cells in vivo and that up‐regulation of VEGF expression may play an important role in this TIMP‐1‐mediated, growth‐stimulating effect. Int. J. Cancer 75:81–87, 1998.Published 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.