Stat3 and MMP7 Contribute to Pancreatic Ductal Adenocarcinoma Initiation and Progression

Akihisa Fukuda, Sam C. Wang, John P. Morris, Alexandra E. Folias, Angela Liou, Grace E. Kim, Shizuo Akira, Kenneth M. Boucher, Matthew A. Firpo, Sean J. Mulvihill, Matthias Hebrok

Research output: Contribution to journalArticle

332 Scopus citations

Abstract

Chronic pancreatitis is a well-known risk factor for pancreatic ductal adenocarcinoma (PDA) development in humans, and inflammation promotes PDA initiation and progression in mouse models of the disease. However, the mechanistic link between inflammatory damage and PDA initiation is unclear. Using a Kras-driven mouse model of PDA, we establish that the inflammatory mediator Stat3 is a critical component of spontaneous and pancreatitis-accelerated PDA precursor formation and supports cell proliferation, metaplasia-associated inflammation, and MMP7 expression during neoplastic development. Furthermore, we show that Stat3 signaling enforces MMP7 expression in PDA cells and that MMP7 deletion limits tumor size and metastasis in mice. Finally, we demonstrate that serum MMP7 level in human patients with PDA correlated with metastatic disease and survival.

Original languageEnglish (US)
Pages (from-to)441-455
Number of pages15
JournalCancer Cell
Volume19
Issue number4
DOIs
StatePublished - Apr 12 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Fukuda, A., Wang, S. C., Morris, J. P., Folias, A. E., Liou, A., Kim, G. E., Akira, S., Boucher, K. M., Firpo, M. A., Mulvihill, S. J., & Hebrok, M. (2011). Stat3 and MMP7 Contribute to Pancreatic Ductal Adenocarcinoma Initiation and Progression. Cancer Cell, 19(4), 441-455. https://doi.org/10.1016/j.ccr.2011.03.002