Abrogation of the interaction between osteopontin and αvβ3 integrin reduces tumor growth of human lung cancer cells in mice
Abrogation of the interaction between osteopontin and αvβ3 integrin reduces tumor growth of human lung cancer cells in mice
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DOI：
10.1016/j.lungcan.2007.03.019
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发表时间：
2007-09-01
期刊：
影响因子：
5.3
通讯作者：
Takahashi, Kazuhisa
中科院分区：
文献类型：
--
作者：
Cui, Ri;Takahashi, Fumiyuki;Takahashi, Kazuhisa
骨桥蛋白（OPN）是一种多功能细胞因子，通过与α v β 3整合素相互作用参与细胞信号转导。最近的症状。研究表明，OPN表达与肺癌患者的肿瘤进展和不良预后相关。然而，骨桥蛋白在人肺癌中的生物学作用尚未明确。本研究的目的是调查和提供证据的因果关系。骨桥蛋白在人肺癌肿瘤生长和血管生成中的作用。本研究从不表达内源性OPN mRNA的人肿瘤细胞系SBC-3中获得了稳定的OPN转染细胞。为了研究骨桥蛋白（OPN）对人肺癌细胞生长的影响，我们将OPN过表达的SBC-3细胞（SBC-3/OPN）和对照细胞（SBC-3/NEO）分别注射到裸鼠皮下。OPN基因转染显著增加小鼠体内肿瘤生长和SBC-3细胞的新血管形成。OPN的这些体内作用在给予抗α v β 3整合素单肽时被显著抑制。抗体或抗血管生成剂TNP-470。重组OPN蛋白对人脐静脉内皮细胞增殖有促进作用。（HUVEC）增殖，并且这种增强在添加抗α v β 3整联蛋白抗体的情况下被显著抑制。总之，这些结果表明，OPN通过与α v β 3整合素相互作用，在体内对人肺癌细胞的肿瘤生长和血管生成起着至关重要的作用。靶向OPN和UvP 3整合素之间的相互作用可能对未来肺癌患者抗血管生成治疗药物的开发有效。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Osteopontin (OPN) is a multifunctional cytokine involved in celt signaling by interacting with alpha v beta 3 integrins. Recent ctinical. studies have indicated that OPN expression is associated with tumor progression and poor prognosis among patients with Lung cancer. However, the biological rote of OPN in human tung cancer has not yet been well-defined. The purpose of this study is to investigate and provide evidence for the causal. role of OPN regarding tumor growth and angiogenesis in human lung cancer. In this study, we developed a stable OPN transfectant from human tung cancer cett line SBC-3 which does not express the intrinsic OPN mRNA. To reveal the in vivo effect of OPN on tumor growth of human Lung cancer, we subcutaneously injected OPN-overexpressing SBC-3 celLs (SBC-3/OPN) and control cells (SBC-3/NEO) into the nude mice. Transfection with the OPN gene significantly increased in vivo tumor growth and neovascularization of SBC-3 ceILs in mice. These in vivo effects of OPN were markedly suppressed with administration of anti-alpha v beta 3 integrin monoctonal. antibody or anti-angiogenic agent, TNP-470. Furthermore, recombinant OPN protein enhanced human umbilical vein enclotheiiat cell. (HUVEC) proliferation in vitro, and this enhancement was significantly inhibited with the addition of anti-alpha v beta 3 integrin antibody. Taken together, these results suggest that OPN plays a crucial rote for tumor growth and angiogenesis of human lung cancer cells in vivo by interacting with alpha v beta 3 integrin. Targeting the interaction between OPN and UvP3 integrin could be effective for future development of anti-angiogenic therapeutic agents for patients with lung cancer. (c) 2007 Elsevier Ireland Ltd. All rights reserved.