Vascular endothelial growth factor and signaling in the prostate:: more than angiogenesis

被引:46
作者
Chevalier, S
Defoy, I
Lacoste, J
Hamel, L
Guy, L
Bégin, LR
Aprikian, AG
机构
[1] McGill Univ, Res Inst, Dept Surg, Urol Oncol Res Grp,Hlth Ctr, Montreal, PQ H3G 1A4, Canada
[2] Univ Montreal, Div Biomed Sci, Montreal, PQ, Canada
[3] Gabriel Montpied Hosp, Dept Urol, Clermont Ferrand, France
[4] Hop Sacre Coeur, Dept Pathol, Montreal, PQ H4J 1C5, Canada
基金
加拿大健康研究院;
关键词
vascular endothelial growth factor; vascular endothelial growth factor receptor; focal adhesion kinase; neuroendocrine differentiation; angiogenesis; motility; prostate cancer;
D O I
10.1016/S0303-7207(01)00728-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In cloning tyrosine kinase genes in dog prostate cells. a fragment of the vascular endothelial growth factor (VEGF) receptor 1 or Flt-1 was sequenced. To test for a functional protein, Flt-1 antibodies were used to probe immunoprecipitated tyrosine phosphorylated proteins. Western blotting revealed a major 170-180 kDa band and a few bands below 116 kDa in dog prostate and human prostatic carcinoma PC-3 cells. with higher levels in PC-3. Similar results were obtained with human placental membranes used as a source of Flt-1. That the major Flt-1 tyrosine phosphorylated protein was likely VEGF-RI and part of VEGF signaling pathways was shown by enhanced level of only this protein when PC-3 cells were exposed to VEGF. Accordingly specific cell surface receptor complexes, displaced by VEGF but not EGF and compatible with Flt-1 in size, were revealed by chemical cross-linking after 121 I-VEGF binding. Similarly to the prostatic neuroproduct, gastrin-releasing peptide,bombesin, VEGF directly triggered the tyrosine phosphorylation of focal adhesion kinase and stimulated PC-3 cell motility. The titration of prostate tissue sections with VEGF-A antibodies revealed a confined staining in chromogranin A and/or serotonin positive neuroendocrine (NE) cells, including in primary tumors and lymph node metastases. Given that NE differentiation is associated with advanced disease, that NE cells are a significant source of VEGF in prostatic tumors, and that VEGF directly act on prostate cancer cells in vitro, VEGF-A may be more than angiogenic in prostate cancer and hence favor progression by affecting tumor cells. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:169 / 179
页数:11
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