PDGF-C Mediates the Angiogenic and Tumorigenic Properties of Fibroblasts Associated with Tumors Refractory to Anti-VEGF Treatment

被引：580

作者：

Crawford, Yongping ^{[1
]}

Kasman, Ian ^{[1
]}

Yu, Lanlan ^{[1
]}

Zhong, Cuiling ^{[1
]}

Wu, Xiumin ^{[1
]}

Modrusan, Zora ^{[1
]}

Kaminker, Josh ^{[1
]}

Ferrara, Napoleone ^{[1
]}

机构：

[1] Genentech Inc, San Francisco, CA 94080 USA

来源：

CANCER CELL | 2009年 / 15卷 / 01期

关键词：

ENDOTHELIAL GROWTH-FACTOR; HUMAN BREAST; STROMAL FIBROBLASTS; INHIBITS GROWTH; ALPHA-RECEPTOR; MYELOID CELLS; CANCER; EXPRESSION; TISSUES; FAMILY;

D O I：

10.1016/j.ccr.2008.12.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Tumor- or cancer-associated fibroblasts (TAFs or CAFs) from different tumors exhibit distinct angiogenic and tumorigenic properties. Unlike normal skin fibroblasts or TAFs from TIB6 tumors that are sensitive to anti-VEGF treatment (TAF-TIB6), TAFs from resistant EL4 tumors (TAF-EL4) can stimulate TIB6 tumor growth even when VEGF is inhibited. We show that platelet-derived growth factor C (PDGF-C) is upregulated in TAFs from resistant tumors. PDGF-C-neutralizing antibodies blocked the angiogenesis induced by such TAFs in vivo, slowed the growth of EL4 and admixture (TAF-EL4 + TIB6) tumors, and exhibited additive effects with anti-VEGF-A antibodies. Hence, our data reveal an additional mechanism for TAF-mediated tumorigenesis and suggest that some tumors may overcome inhibition of VEGF-mediated angiogenesis through upregulation of PDGF-C.

引用

页码：21 / 34

页数：14

共 54 条

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