PDGF-C Mediates the Angiogenic and Tumorigenic Properties of Fibroblasts Associated with Tumors Refractory to Anti-VEGF Treatment
PDGF-C Mediates the Angiogenic and Tumorigenic Properties of Fibroblasts Associated with Tumors Refractory to Anti-VEGF Treatment
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DOI：
10.1016/j.ccr.2008.12.004
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发表时间：
2009-01-06
期刊：
影响因子：
50.3
通讯作者：
Ferrara, Napoleone
中科院分区：
文献类型：
--
作者：
Crawford, Yongping;Kasman, Ian;Ferrara, Napoleone
来自不同肿瘤的肿瘤或癌症相关成纤维细胞（TAF或CAF）表现出不同的血管生成和致瘤特性。与对抗VEGF治疗敏感的正常皮肤成纤维细胞或来自TIB 6肿瘤的TAF（TAF-TIB 6）不同，来自抗性EL 4肿瘤的TAF（TAF-EL 4）即使在VEGF被抑制时也可以刺激TIB 6肿瘤生长。我们发现，血小板衍生生长因子C（PDGF-C）在耐药肿瘤的TAFs中上调。PDGF-C-中和抗体在体内阻断了由这种TAF诱导的血管生成，减缓了EL 4和混合物（TAF-EL 4 + TIB 6）肿瘤的生长，并与抗VEGF-A抗体表现出累加效应。因此，我们的数据揭示了TAF介导的肿瘤发生的另一种机制，并表明某些肿瘤可能通过上调PDGF-C来克服VEGF介导的血管生成抑制。
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.