Blockade of MK2 is protective in inflammation-associated colorectal cancer development

被引：32

作者：

Ray, Anita L. ^{[1
]}

Castillo, Eliseo F. ^{[1
]}

Morris, Katherine T. ^{[2
]}

Nofchissey, Robert A. ^{[1
]}

Weston, Lea L. ^{[1
]}

Samedi, Von G. ^{[3
]}

Hanson, Joshua A. ^{[3
]}

Gaestel, Matthias ^{[4
]}

Pinchuk, Irina V. ^{[5
]}

Beswick, Ellen J. ^{[1
]}

机构：

[1] Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA

[2] Univ New Mexico, Dept Surg, Albuquerque, NM 87131 USA

[3] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA

[4] Hannover Med Sch, Dept Biochem, Hannover, Germany

[5] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA

来源：

INTERNATIONAL JOURNAL OF CANCER | 2016年 / 138卷 / 03期

关键词：

MK2; Colorectal Cancer; IL-1; IL-6; TNF-alpha; macrophages; ACTIVATED PROTEIN-KINASE; P38; CELLS; PATHOGENESIS; MACROPHAGES; PATHWAYS; IL-6;

D O I：

10.1002/ijc.29716

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Chronic inflammation is a risk factor for colorectal cancer. The MAPK-activated protein kinase 2 (MK2) pathway controls multiple cellular processes including p38-dependent inflammation. This is the first study to investigate the role of MK2 in development of colitis-associated colon cancer (CAC). Herein, we demonstrate that MK2(-/-) mice are highly resistant to neoplasm development when exposed to AOM/DSS, while wild type (WT) C57BL/6 develop multiple neoplasms with the same treatment. MK2-specific cytokines IL-1, IL-6 and TNF-alpha were substantially decreased in AOM/DSS treated MK2(-/-) mouse colon tissues compared with WT mice, which coincided with a marked decrease in macrophage influx. Restoring MK2-competent macrophages by injecting WT bone marrow derived macrophages into MK2(-/-) mice led to partial restoration of inflammatory cytokine production with AOM/DSS treatment; however, macrophages were not sufficient to induce neoplasm development. These results indicate that MK2 functions as an inflammatory regulator to promote colonic neoplasm development and may be a potential target for CAC.

引用

页码：770 / 775

页数：6

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