Title: Data from Osteopontin Promotes Vascular Endothelial Growth Factor–Dependent Breast Tumor Growth and Angiogenesis via Autocrine and Paracrine Mechanisms
Abstract:<div>Abstract<p>Angiogenesis is the hallmark of cancer, and development of aggressiveness of primary tumor depends on <i>de novo</i> angiogenesis. Here, using multiple <i>...<div>Abstract<p>Angiogenesis is the hallmark of cancer, and development of aggressiveness of primary tumor depends on <i>de novo</i> angiogenesis. Here, using multiple <i>in vitro</i> and <i>in vivo</i> models, we report that osteopontin (OPN) triggers vascular endothelial growth factor (VEGF)–dependent tumor progression and angiogenesis by activating breast tumor kinase (Brk)/nuclear factor–inducing kinase/nuclear factor-κB (NF-κB)/activating transcription factor-4 (ATF-4) signaling cascades through autocrine and paracrine mechanisms in breast cancer system. Our results revealed that both exogenous and tumor-derived OPN play significant roles in VEGF-dependent tumor angiogenesis. Clinical specimen analysis showed that OPN and VEGF expressions correlate with levels of neuropilin-1, Brk, NF-κB, and ATF-4 in different grades of breast cancer. Consequently, OPN plays essential role in two key aspects of tumor progression: VEGF expression by tumor cells and VEGF-stimulated neovascularization. Thus, targeting OPN and its regulated signaling network could be a novel strategy to block tumor angiogenesis and may develop an effective therapeutic approach for the management of breast cancer. [Cancer Res 2008;68(1):152–61]</p></div>Read More