Pro-inflammatory Lymphocytes Promote Breast and Intestinal Cancer

James G. Fox, DVM, Ph.D.
Massachusetts Institute of Technology
P30ES02109

Background: Colorectal cancer is the third most common form of cancer and also the third leading cause of cancer mortality in the United States. Breast cancer is the most common form of cancer in women and strikes one out of every eight women at some point in their lives. There have been numerous research studies that have shown that the risk of both these cancers is reduced in women who regularly take non-steroidal anti-inflammatory drugs, such as aspirin and ibuprofen, suggesting that inflammation contributes to the development of intestinal and breast carcinogenesis in humans. However, there is a lack of good experimental animal models to investigate the link between inflammation and breast cancer.

Advance: A recent study by an NIEHS-supported team of researchers at the Massachusetts Institute of Technology has made progress in the ability to test the inflammation/cancer link. These researchers injected mice genetically prone to develop cancerous intestinal polyps and breast tumors with a specific sub-type of pro-inflammatory T-cells which induced inflammatory bowel disease. As predicted, the injected mice developed many more intestinal polyps than did the non-injected controls. Surprisingly, 70% of the female mice that received the pro-inflammatory T-cells also rapidly developed mammary tumors. There was no evidence of mammary tumor development in the untreated female mice. The investigators went further in experiments in which mice received by pro- and anti-inflammatory T-cells. In these experiments, neither the intestinal polyps nor the mammary tumors developed. Lastly, down regulation of the enzyme cyclooxygenase-2 (COX-2), a known target of non-steroidal anti-inflammatory drugs, was observed coincident with tumor regression.

Implications: These studies define a new model for inflammation-driven mammary tumor development, and represent an important new tool to investigate the inflammation/cancer link. The findings also allude to the broader applicability of anti-inflammatory therapies in the treatment of specific types of cancer that are responsive to COX-2 inhibitors and other non-steroidal anti-inflammatory drugs.

Citation: Rao VP, Poutahidis T, Ge Z, Nambiar PR, Horwitz BH, Fox JG, Erdman SE. Proinflammatory CD4+ CD45RB(hi) lymphocytes promote mammary and intestinal carcinogenesis in Apc(Min/+) mice. Cancer Res. 2006 Jan 1;66(1):57-61.