Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically

被引：353

作者：

Putoczki, Tracy L. ^{[1
,6
]}

Thiem, Stefan ^{[1
]}

Loving, Andrea ^{[1
]}

Busutti, Rita A. ^{[3
,4
,5
]}

Wilson, Nicholas J. ^{[2
]}

Ziegler, Paul K. ^{[7
]}

Nguyen, Paul M. ^{[1
]}

Preaudet, Adele ^{[1
]}

Farid, Ryan ^{[1
]}

Edwards, Kirsten M. ^{[2
]}

Boglev, Yeliz ^{[1
]}

Luwor, Rodney B. ^{[6
]}

Jarnicki, Andrew ^{[1
]}

Horst, David ^{[8
]}

Boussioutas, Alex ^{[3
,4
,5
]}

Heath, Joan K. ^{[1
]}

Sieber, Oliver M. ^{[1
]}

Pleines, Irina ^{[9
]}

Kile, Benjamin T. ^{[9
]}

Nash, Andrew ^{[2
]}

Greten, Florian R. ^{[7
]}

McKenzie, Brent S. ^{[2
]}

Ernst, Matthias ^{[1
,6
]}

机构：

[1] Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia

[2] CSL Ltd, Melbourne, Vic 3050, Australia

[3] Peter MacCallum Canc Ctr, Canc Genet & Genom Lab, East Melbourne, Vic 3002, Australia

[4] Univ Melbourne, Peter MacCallum Canc Ctr, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3010, Australia

[5] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne, Vic 3050, Australia

[6] Univ Melbourne, Royal Melbourne Hosp, Dept Surg, Melbourne, Vic 3050, Australia

[7] Tech Univ Munich, Inst Mol Immunol, D-81675 Munich, Germany

[8] Univ Munich, Inst Pathol, D-80337 Munich, Germany

[9] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia

来源：

CANCER CELL | 2013年 / 24卷 / 02期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

MULTIPLE INTESTINAL NEOPLASIA; LYMPH-NODE METASTASIS; GASTRIC TUMORIGENESIS; SIGNALING PATHWAY; EPITHELIAL-CELLS; RECEPTOR-ALPHA; JAK2; INHIBITOR; MOUSE MODEL; STAT3; CANCER;

D O I：

10.1016/j.ccr.2013.06.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer "hallmarks" through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers.

引用

页码：257 / 271

页数：15

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