Human papillomavirus up-regulates MMP-2 and MMP-9 expression and activity by inducing interleukin-8 in lung adenocarcinomas.
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.
Department of Nursing, College of Medicine & Nursing, Hungkuang University, Taichung, Taiwan, Republic of China.
Ming-Yuh
MY
Shiau
Li-Ching
LC
Fan
Shun-Chun
SC
Yang
Chang-Hui
CH
Tsao
Huei
H
Lee
Ya-Wen
YW
Cheng
Li-Chuan
LC
Lai
Yih-Hsin
YH
Chang
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics / Q000821:virology; D015854:Up-Regulation
D016209:Interleukin-8; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9