Stat3 and MMP7 Contribute to Pancreatic Ductal Adenocarcinoma Initiation and Progression

详细信息    查看全文

• 作者：Akihisa Fukuda¹ ; ⁷ ; Sam  ; C. Wang¹ ; ⁷ ; John  ; P. Morris IV¹ ; Alexandra  ; E. Folias¹ ; Angela Liou¹ ; Grace  ; E. Kim² ; Shizuo Akira³ ; Kenneth  ; M. Boucher⁴ ; ⁶ ; Matthew  ; A. Firpo⁵ ; ⁶ ; Sean  ; J. Mulvihill⁵ ; ⁶ ; Matthias Hebrok¹ ; ^{mhebrok@diabetes.ucsf.edu}
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：12 April 2011
• 年：2011
• 卷：19
• 期：4
• 页码：441-455
• 全文大小：3656 K

文摘

Summary

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.