Inflammation Contributes To Colon Cancer

Main Category: Colorectal Cancer
Also Included In: Cancer / Oncology;  GastroIntestinal / Gastroenterology
Article Date: 03 Jan 2009 - 0:00 PDT

email to a friend   printer friendly   opinions  

Researchers led by Dr. Brian Iritani at The University of Washington found that mice that lack the immune inhibitory molecule Smad3 are acutely sensitive to both bacterially-induced inflammation and cancer. They report these findings in the January 2009 issue of The American Journal of Pathology.

Bacteria contribute to the development of certain cancers, in some measure, by stimulating chronic inflammation. Absence of a molecule that inhibits inflammation, Smad3, may therefore increase susceptibility to colon cancer.

To examine whether Smad3 signaling contributes to development of colon cancer, Maggio-Price et al examined mice deficient in Smad3 that lack of adaptive immune responses. They found that these mice are acutely sensitive to bacterially-induced inflammation and cancer due to both deficient T regulatory cell function and increased expression of proinflammatory cytokines. Through increased expression of both pro-oncogenic and anti-apoptotic proteins, epithelial cells in colonic tissues underwent both enhanced proliferation and survival.

"That the inflammatory response to microorganisms is a key event in these results reveals important 'tumor-suppressive' functions for Smad3 in T effector cells, T regulatory cells, and intestinal epithelial cells, all of which may normally limit the development of colon cancer in response to bacterial inflammation," explains Dr. Iritani's group.

Maggio-Price L, Treuting P, Bielefeldt-Ohmann H, Seamons A, Drivdahl R, Zeng W, Lai L-H, Huycke M, Phelps S, Brabb T1, Iritani BM
"Bacterial infection of Smad3/Rag2 double-null mice with TGF beta dysregulation as a model for studying inflammation-associated colon cancer.
Am J Pathol 2009, 174:317-329

American Journal of Pathology, official journal of the American Society for Investigative Pathology, seeks to publish high-quality, original papers on the cellular and molecular biology of disease. The editors accept manuscripts that advance basic and translational knowledge of the pathogenesis, classification, diagnosis, and mechanisms of disease, without preference for a specific analytic method. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, animal, biological, chemical, and immunological approaches in conjunction with morphology.

Source
Angela Colmone
American Journal of Pathology

• Additional
• References
• Citations