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	Overexpression of Platelet-Derived Growth Factor-BB Increases Tumor Pericyte Content via Stromal-Derived Factor-1 alpha/CXCR4 Axis
	Song, Nan ; Huang, Yujie ; Shi, Hubing ; Yuan, Shaopeng ; Ding, Yanping ; Song, Xiaomin ; Fu, Yan ; Luo, Yongzhang
	2010-10-12 ; 2010-10-12
关键词	ENDOTHELIAL-CELLS PDGF-B VESSEL MATURATION PROGENITOR CELLS ANGIOGENESIS RECEPTOR RECRUITMENT EXPRESSION INDUCTION HYPOXIA Oncology
中文摘要	Platelet-derived growth factor-BB (PDGF-BB) is a well-characterized growth factor displaying potent biological effects on angiogenesis. Recent studies reveal that overexpression of PDGF-BB within tumors results in increased pericyte coverage, suggesting that PDGF-BB signaling is also essential for the cancerous pericyte recruitment process. However, the molecular mechanism underlying this regulation remains obscure. In the current study, we show that tumor-derived PDGF-BB induces SDF-1 alpha expression in endothelial cells (EC), resulting in the formation of SDF-1 alpha chemotaxis gradient, which coincides with the PDGF-BB-induced pericyte recruitment during angiogenesis. PDGF-BB dramatically upregulates SDF-1 alpha secretion through the activation of PDGFR beta in tumor-associated ECs, whereas this up-regulation can be substantially inhibited by either blockade of the phosphatidylinositol 3-kinase/Akt/mTOR pathway with chemical inhibitors or the inactivation of HIF-1 alpha through small interfering RNA interference. On the other hand, we reveal that SDF-1 alpha can increase pericytes motility in vitro. Blockade of the SDF-1 alpha/CXCR4 axis prevents the PDGF-BB-induced pericyte recruitment not only in three in vitro recruitment models but also in the PDGF-BB-overexpressing tumor xenograft models. These results highlight that the involvement of SDF-1 alpha/CXCR4 axis is essential for the pericyte recruitment within the PDGF-BB-overexpressing tumors and raise the possibility that blockade of the SDF-1 alpha/CXCR4 axis may provide a therapeutic synergy with antiangiogenic molecules that selectively target ECs. [Cancer Res 2009;69(15):6057-64]
语种	英语 ; 英语
出版者	AMER ASSOC CANCER RESEARCH ; PHILADELPHIA ; 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/81806]
专题	清华大学
推荐引用方式 GB/T 7714	Song, Nan,Huang, Yujie,Shi, Hubing,et al. Overexpression of Platelet-Derived Growth Factor-BB Increases Tumor Pericyte Content via Stromal-Derived Factor-1 alpha/CXCR4 Axis[J],2010, 2010.
APA	Song, Nan.,Huang, Yujie.,Shi, Hubing.,Yuan, Shaopeng.,Ding, Yanping.,...&Luo, Yongzhang.(2010).Overexpression of Platelet-Derived Growth Factor-BB Increases Tumor Pericyte Content via Stromal-Derived Factor-1 alpha/CXCR4 Axis..
MLA	Song, Nan,et al."Overexpression of Platelet-Derived Growth Factor-BB Increases Tumor Pericyte Content via Stromal-Derived Factor-1 alpha/CXCR4 Axis".(2010).

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