血小板衍生生长因子C（PDGF-C）介导了与抗血管内皮生长因子（VEGF）治疗难治性肿瘤相关的成纤维细胞的血管生成和致瘤特性。

PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment.

作者信息

Crawford Yongping, Kasman Ian, Yu Lanlan, Zhong Cuiling, Wu Xiumin, Modrusan Zora, Kaminker Josh, Ferrara Napoleone

机构信息

Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA.

出版信息

Cancer Cell. 2009 Jan 6;15(1):21-34. doi: 10.1016/j.ccr.2008.12.004.

DOI:10.1016/j.ccr.2008.12.004

PMID:19111878

Abstract

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.

摘要

来自不同肿瘤的肿瘤相关成纤维细胞（TAF或CAF）具有不同的血管生成和致瘤特性。与正常皮肤成纤维细胞或对抗VEGF治疗敏感的TIB6肿瘤来源的TAF（TAF-TIB6）不同，来自耐药性EL4肿瘤的TAF（TAF-EL4）即使在VEGF被抑制时也能刺激TIB6肿瘤生长。我们发现血小板衍生生长因子C（PDGF-C）在耐药肿瘤来源的TAF中上调。PDGF-C中和抗体在体内阻断了此类TAF诱导的血管生成，减缓了EL4和混合肿瘤（TAF-EL4 + TIB6）的生长，并与抗VEGF-A抗体表现出相加效应。因此，我们的数据揭示了TAF介导的肿瘤发生的另一种机制，并表明一些肿瘤可能通过上调PDGF-C来克服对VEGF介导的血管生成的抑制。