Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer

被引:115
作者
Toi, M
Bando, H
Ogawa, T
Muta, M
Hornig, C
Weich, HA
机构
[1] Tokyo Metropolitan Komagome Hosp, Breast Unit, Bunkyo Ku, Tokyo 113, Japan
[2] RELIATech GmbH, Braunschweig, Germany
[3] German Res Ctr Biotechnol, Braunschweig, Germany
关键词
soluble form vascular endothelial growth factor receptor; vascular endothelial growth factor; breast cancer;
D O I
10.1002/ijc.10121
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Angiogenesis, the formation of new blood vessels, is controlled by a balance between positive and negative endothelial regulatory factors. Soluble vascular endothelial growth factor receptor-1 (sVEGFR1), a naturally occurring soluble form of VEGFR1, is a negative counterpart of the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulators in human tumor angiogenesis. In our study, we examined the expression of sVEGFR1 in 110 primary breast carcinomas, and assessed its clinical significance. Ninety-four of 110 tumors showed greater than or equal to0.1 ng/mg protein of sVEGFR1 (range: 0.1-6.9 ng/mg protein; median: 1.03 ng/mg protein) as determined by a specific enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis confirmed the presence of sVEGFR1 in breast tumor tissues. The levels of sVEGFR1 were correlated significantly with the levels of VEGF. There was no significant correlation between the levels of sVEGFR1 and any clinico-pathological factors including age, menopause, nodal involvement and hormone receptor status. A univariate prognosis analysis showed that the intra-tumoral VEGF status, as determined by ELISA, was a significant prognostic indicator, but sVEGFR1 status was not. In the combined analysis, however, the ratio of sVEGFR1 and VEGF levels provided more statistically significant prognostic value than VEGF status alone. Tumors in which the sVEGFR1 levels exceeded VEGF levels 10-fold had a markedly favorable prognosis. Multivariate analysis also demonstrated that the ratio of sVEGFR1 and VEGF was an independent prognostic indicator after nodal status. In conclusion, sVEGFR1, an intrinsic inhibitor of VEGF, frequently co-expressed with VEGF in primary breast cancer tissues. The intratumoral balance between sVEGFR1 and VEGF levels might be crucial for the progression of breast cancer. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:14 / 18
页数:5
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