Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong, People's Republic of China.
Cancer Lett. 2011 Dec 8;311(2):160-70. doi: 10.1016/j.canlet.2011.07.012. Epub 2011 Jul 22.
HPV-16 infection may play an important role in the development of non-small cell lung cancer (NSCLC) among never-smokers. Due to the critical role of angiogenesis in NSCLC development, we describe here the effect of HPV-16 oncoproteins on angiogenesis in NSCLC and the underlying mechanisms. We found that overexpression of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted angiogenesis both in vitro and in vivo, and correspondingly, an enhanced expression of HIF-1α and VEGF, important pro-angiogenic factors in tumor angiogenesis. Meanwhile, overexpression of HPV-16 oncoproteins also led to HIF-1α-dependent increases in the secretion of several other pro-angiogenic factors, including IL-8. Our findings suggest that HPV-16 oncoproteins contribute to the development of NSCLC possibly by promoting HIF-1α/VEGF-mediated tumor angiogenesis.
HPV-16 感染可能在从不吸烟的非小细胞肺癌（NSCLC）的发展中发挥重要作用。由于血管生成在 NSCLC 发展中的关键作用，我们在这里描述了 HPV-16 致癌蛋白对 NSCLC 血管生成的影响及其潜在机制。我们发现，HPV-16 E6 和 E7 致癌蛋白在 NSCLC 细胞中的过度表达显著促进了体外和体内的血管生成，相应地，HIF-1α 和 VEGF 的表达增强，HIF-1α 和 VEGF 是肿瘤血管生成中重要的促血管生成因子。同时，HPV-16 致癌蛋白的过度表达也导致了 HIF-1α 依赖性的几种其他促血管生成因子的分泌增加，包括 IL-8。我们的研究结果表明，HPV-16 致癌蛋白可能通过促进 HIF-1α/VEGF 介导的肿瘤血管生成来促进 NSCLC 的发展。
