Stat3 and MMP7 Contribute to Pancreatic Ductal Adenocarcinoma Initiation and Progression

被引：428

作者：

Fukuda, Akihisa ^{[1
]}

Wang, Sam C. ^{[1
]}

Morris, John P. ^{[1
]}

Folias, Alexandra E. ^{[1
]}

Liou, Angela ^{[1
]}

Kim, Grace E. ^{[2
]}

Akira, Shizuo ^{[6
]}

Boucher, Kenneth M. ^{[3
,5
]}

Firpo, Matthew A. ^{[4
,5
]}

Mulvihill, Sean J. ^{[4
,5
]}

Hebrok, Matthias ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Ctr Diabet, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA

[3] Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84115 USA

[4] Univ Utah, Dept Surg, Salt Lake City, UT 84115 USA

[5] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84115 USA

[6] Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, Osaka 5650871, Japan

来源：

CANCER CELL | 2011年 / 19卷 / 04期

基金：

日本学术振兴会;

关键词：

MATRIX METALLOPROTEINASES; EPITHELIAL-CELLS; ACINAR-CELLS; EXPRESSION; CANCER; ACTIVATION; INHIBITOR; INFLAMMATION; PATHWAY; TISSUE;

D O I：

10.1016/j.ccr.2011.03.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：441 / 455

页数：15

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