Human Papillomavirus Up-Regulates MMP-2 and MMP-9 Expression and Activity by Inducing Interleukin-8 in Lung Adenocarcinomas

Ming Yuh Shiau, Li Ching Fan, Shun Chun Yang, Chang Hui Tsao, Huei Lee, Ya Wen Cheng, Li Chuan Lai, Yih Hsin Chang

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18 Citations (Scopus)

Abstract

Human papillomavirus (HPV) infection is associated with non-smoking female lung cancer. Our previous report demonstrated that HPV 16 promotes lung tumor cell progression by up-regulating interleukin-17 (IL-17). IL-17 and its downstream signaling mediator, interleukin-8 (IL-8), have been implicated to modulate a variety of pro-angiogenic factors and play important roles in tumor angiogenesis and metastasis. Accordingly, we hypothesized that HPV infection may potentiate tumorigenic and metastatic characteristics of the infected cells through IL-8. The goal of the present study was to determine whether HPV infection in lung adenocarcinoma cells can promote the expression of IL-8 and metalloproteinases (MMPs) to make the transformed cells equipped with angiogenic and metastatic characteristics. The expression of IL-8 and MMPs in HPV 16 E6-transfected H1299 cells was analyzed to examine the hypothesis. HPV 16 E6 up-regulates pro-angiogenic MMP-2 and MMP-9 through inducing IL-8 expression in lung cancer cells. The results indicate that, in addition to cell proliferation-related machinery, HPV infection promotes the expression and activities of angiogenic and metastatic molecules in lung adenocarcinoma cells. The cytokines induced by HPV infection may work together to confer the malignant and tumorigenic potentials on the infected cells by promoting machineries of growth, angiogenic and metastatic characteristics.

Original languageEnglish
Article numbere54423
JournalPLoS One
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 21 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Shiau, M. Y., Fan, L. C., Yang, S. C., Tsao, C. H., Lee, H., Cheng, Y. W., Lai, L. C., & Chang, Y. H. (2013). Human Papillomavirus Up-Regulates MMP-2 and MMP-9 Expression and Activity by Inducing Interleukin-8 in Lung Adenocarcinomas. PLoS One, 8(1), [e54423]. https://doi.org/10.1371/journal.pone.0054423