Journal
CANCER LETTERS
Volume 311, Issue 2, Pages 160-170Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.07.012
Keywords
Human papillomavirus (HPV); Non-small cell lung cancer; Angiogenesis; HIF-1 alpha; VEGF
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Funding
- National Natural Science Foundation of China [30872944, 81073103]
- Science and Technology of Guangdong Province [2009B030801330]
- Science and Technology of Dongguan City [2008108101029]
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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-1 alpha and VEGF, important pro-angiogenic factors in tumor angiogenesis. Meanwhile, overexpression of HPV-16 oncoproteins also led to HIF-1 alpha-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-1 alpha/VEGF-mediated tumor angiogenesis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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