Pancreatic stellate cells radioprotect pancreatic cancer cells through β1-integrin signaling.
Pancreatic stellate cells radioprotect pancreatic cancer cells through β1-integrin signaling.
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DOI：
10.1158/0008-5472.can-10-1633
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发表时间：
2011-05-15
期刊：
影响因子：
11.2
通讯作者：
Brunner TB
中科院分区：
文献类型：
--
作者：
Mantoni TS;Lunardi S;Al-Assar O;Masamune A;Brunner TB
胰腺导管腺癌(PDAC)的特点是强烈的促结缔组织增生性反应，间质间质通常占肿瘤体积的一半以上。胰腺星状细胞(PSC)是促结缔组织增生症的中枢介质。越来越多的证据表明，结缔组织增生症是导致PDAC治疗反应差的原因之一。我们发现，在直接共培养的胰腺癌细胞(PCC)中，PSC促进辐射防护和刺激增殖。我们的体内研究表明，PSC依赖于对单次剂量和分次辐射的放射保护。取消PSC1-整合素信号通路可取消β介导的辐射防护作用。此外，这种效应不依赖于PI3K，但依赖于FAK。综上所述，我们首次证明了PSC以一种β-1整合素依赖的方式促进了PCC的辐射防护。
Pancreatic ductal adenocarcinoma (PDAC) is characterised by a strong desmoplastic reaction where the stromal compartment often accounts for more than half of the tumor volume. Pancreatic stellate cells (PSC) are a central mediator of desmoplasia. There is increasing evidence that the desmoplasia is contributing to the poor therapeutic response of PDAC. We show that PSC promote radioprotection and stimulate proliferation in pancreatic cancer cells (PCC) in direct coculture. Our in vivo studies demonstrate PSC dependent radioprotection in response to a single dose and to fractionated radiation. Abrogating β1-integrin signaling abolishes the PSC mediated radioprotection in PCC. Furthermore, this effect is independent of PI3K, but dependent on FAK. Taken together we demonstrate for the first time that PSC promote radioprotection of PCC in a β1-integrin dependent manner.