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IL-6 Regulates MMP-10 Expression via JAK2/STAT3 Signaling Pathway in a Human Lung Adenocarcinoma Cell Line

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Author

  • Xiaoying Zhang
  • Peiji Yin
  • Dongmei Di
  • Guanghua Luo
  • Lu Zheng
  • Jiang Wei
  • Jun Zhang
  • Yuanping Shi
  • Jichen Zhang
  • Ning Xu

Summary, in English

We previously reported that matrix metalloproteinase (MMP)-10 mRNA levels were significantly lower in tumor tissues than in adjacent normal tissues in human non-small cell lung cancer (NSCLC), whereas protein levels of MMP-10 were higher in the tumor tissues than the adjacent tissues. The mechanism of this divergence is still unknown. In the present stud), the role of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) on interleukin (IL)-6 mediated regulation of MMP-10 expression was investigated in a human lung adenocarcinoma cell line (A549 cells) and the molecular regulatory mechanism of MMP-10 expression was explored. A549 cells were stimulated by different concentrations of IL-6 with or without AG490, a specific JAK2 inhibitor. It was demonstrated that IL-6 moderately reduced the MMP-10 mRNA levels, whereas it significantly enhanced the MMP-10 protein mass in the A549 cells. This phenomenon mimicked the divergence of mRNA level and protein mass of MMP-10 in human NSCLC. Moreover, the present study indicated that IL-6 regulation of MMP-10 expression was via the JAK2/STAT3 pathway. STAT3 mRNA levels were significantly increased when the cells were treated with IL-6, whereas when AG490 (50 mu M) was added to the cell cultures, IL-6-induced increase of STAT3 mRNA levels was abolished. Meanwhile, AG490 blocked the IL-6-induced inhibition of MMP-10 mRNA as well as blocking the IL-6-induced increase of MMP-10 protein mass in the A549 cells. Neither IL-6 nor AG490 influenced JAK2 mRNA levels in the A549 cell cultures. It is concluded that the JAK2/STAT3 pathway is involved in the IL-6-mediated regulation of MMP-10, and IL-6 can moderately reduce MMP-10 mRNA levels and strongly increase MMP-10 protein mass in human lung adenocarcinoma A549 cells. Contrasting effects of IL-6 on MMP-10 mRNA level and protein concentration in A549 cells may partially explain the divergence of MMP-10 mRNA level and protein mass in human NSCLC.

Publishing year

2009

Language

English

Pages

4497-4501

Publication/Series

Anticancer research

Volume

29

Issue

11

Document type

Journal article

Publisher

International Institute of Cancer Research

Topic

  • Cancer and Oncology

Keywords

  • JAK2/STAT3
  • MMP-10
  • IL-6
  • lung cancer

Status

Published

ISBN/ISSN/Other

  • ISSN: 1791-7530