Osteopontin (OPN) is a multifunctional
cytokine involved in cell signaling by interacting with alphavbeta3
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-alphavbeta3
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-alphavbeta3
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
alphavbeta3 integrin. Targeting the interaction between OPN and
alphavbeta3 integrin could be effective for future development of anti-angiogenic therapeutic agents for patients with
lung cancer.