Abrogation of the interaction between osteopontin and αvβ3 integrin reduces tumor growth of human lung cancer cells in mice
- 作者：Ri Cui ; Fumiyuki Takahashi ; Rina Ohashi ; Tao Gu ; Masakata Yoshioka ; Kazuto Nishio ; Yuichiro Ohe ; Shigeru Tominaga ; Yumiko Takagi ; Shinichi Sasaki ; Yoshinosuke Fukuchi ; Kazuhisa Takahashi
- 关键词：Osteopontin ; Angiogenesis ; α ; vβ ; 3 integrin ; Tumor growth ; Lung cancer
- 刊名：Lung Cancer
- 出版年：2007
- 期刊代码：187_01695002
- 类别：med
- 出版时间：September 2007
- 卷：57
- 期：3
- 页码：302-310
- 文件大小：620 K
摘要
Osteopontin (OPN) is a multifunctional cytokine involved in cell signaling by interacting with αvβ3 integrins. Recent clinical studies have indicated that OPN expression is associated with tumor progression and poor prognosis among patients with lung cancer. However, the biological role of OPN in human lung 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 lung cancer cell 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 cells in mice. These in vivo effects of OPN were markedly suppressed with administration of anti-αvβ3 integrin monoclonal antibody or anti-angiogenic agent, TNP-470. Furthermore, recombinant OPN protein enhanced human umbilical vein endothelial cell (HUVEC) proliferation in vitro, and this enhancement was significantly inhibited with the addition of anti-αvβ3 integrin antibody. Taken together, these results suggest that OPN plays a crucial role for tumor growth and angiogenesis of human lung cancer cells in vivo by interacting with αvβ3 integrin. Targeting the interaction between OPN and αvβ3 integrin could be effective for future development of anti-angiogenic therapeutic agents for patients with lung cancer.