Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer
Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer
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DOI：
10.3892/ijo.2016.3374
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发表时间：
2016-04-01
影响因子：
5.2
通讯作者：
Nakamura, Masafumi
中科院分区：
文献类型：
--
作者：
Horioka, Kohei;Ohuchida, Kenoki;Nakamura, Masafumi
胰腺星状细胞（PSCs）通过与癌细胞相互作用并产生细胞外基质（ECM）而增强胰腺癌的恶性行为。迄今为止，已经尝试了几种针对胰腺癌的基质靶向疗法，但这些疗法仍然没有实际应用。在基质细胞中表达的整合素参与几种器官的纤维化，以及促进肿瘤恶性。我们研究了PSC中表达的CD51（也称为整合素α V）是否与胰腺癌的基质形成和肿瘤恶性程度的增强相关。我们还评估了抑制PSC中的CD51对胰腺癌的影响。CD51在胰腺癌间质中的高表达与淋巴结转移（P=0.025）、病理切缘阳性（P = 0.025）和患者生存期缩短（P=0.043）有关。慢病毒介导的CD51短发夹RNA敲低降低了PSC的增殖和迁移。实时定量聚合酶链反应显示，CD51基因敲低可降低PSC中ECM和肿瘤间质相互作用相关基因的表达水平。在胰腺癌细胞和PSC的共植入模型中，PSC中的CD51敲低抑制了体内肿瘤生长（P
Pancreatic stellate cells (PSCs) enhance the malignant behavior of pancreatic cancer by interacting with cancer cells and producing extracellular matrix (ECM). To date, several stroma-targeted therapies for pancreatic cancer have been attempted, but these therapies are still not in practical use. Integrins expressed in stromal cells are involved in fibrosis of several organs, as well as promoting tumor malignancy. We investigated whether CD51, also known as integrin alpha V, expressed in PSCs was associated with stromal formation of pancreatic cancer and enhancement of tumor malignancy. We also assessed the effects of suppression of CD51 in PSCs on pancreatic cancer. Immunohistochemistry for CD51 in resected pancreatic cancer tissues showed that high expression of CD51 in the tumor stroma was associated with lymph node metastasis (P=0.025), positive pathologic margin (P=0.025), and shorter patient survival times (P=0.043). Lentivirus-mediated short hairpin RNA knockdown of CD51 decreased the proliferation and migration of PSCs. Quantitative real-time polymerase chain reaction showed that expression levels of genes related with ECM and tumor-stromal interactions were decreased by CD51 knockdown in PSCs. In a co-implantation model of pancreatic cancer cells and PSCs, tumor growth in vivo was inhibited by CD51 knockdown in PSCs (P