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

Anita L. Ray, Eliseo F. Castillo, Katherine T. Morris, Robert A. Nofchissey, Lea L. Weston, Von G. Samedi, Joshua A. Hanson, Matthias Gaestel, Iryna Pinchuk, Ellen J. Beswick

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15 Scopus citations

Abstract

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-α 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. What's new? The role of inflammation in cancer development is intriguing, especially in colitis-associated colon cancer. Here the authors examine the role of MAP kinase-activated protein kinase 2 (MK2) in this process. They show that MK2-/- mice produce less cytokines (IL-1, IL-6 and TNF-alpha) and are highly resistant to cancer development, a process only partially reversed by transfusion of wildtype macrophages. The data identify MK2 as an inflammatory regulator in colon cancer development and a possible new drug target for this disease.

Original languageEnglish (US)
Pages (from-to)770-775
Number of pages6
JournalInternational Journal of Cancer
Volume138
Issue number3
DOIs
StatePublished - Feb 1 2016

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Keywords

  • Colorectal Cancer
  • IL-1
  • IL-6
  • macrophages
  • MK2
  • TNF-α

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ray, A. L., Castillo, E. F., Morris, K. T., Nofchissey, R. A., Weston, L. L., Samedi, V. G., Hanson, J. A., Gaestel, M., Pinchuk, I., & Beswick, E. J. (2016). Blockade of MK2 is protective in inflammation-associated colorectal cancer development. International Journal of Cancer, 138(3), 770-775. https://doi.org/10.1002/ijc.29716