Inflammation Found Linked to Cancer

When IKK beta was deleted, the cancer incidence and tumor growth in mice were decreased nearly 80%. IKK beta is required for activation of a protein called nuclear factor kappa B (NF-kB) that acts as a master switch to turn on inflammation in response to a bacterial or viral infection. In epithelial cells, NF-kB promotes the development of cancer through the inhibition of apoptosis, not through inflammation. In myloid cells, NF-kB causes the expression of pro-inflammatory molecules that stimulate the division of genetically altered epithelial cells and thereby increase tumor size.

Since recurrent inflammation and chronic infections contribute to a large number of different cancers, the researchers chose one of these cancers, CAC (colitis-associated cancer), as their model for study.

"In response to chronic infection, the interplay between immune cells and the epithelial cells of the intestinal tract, which becomes genetically transformed to give rise to malignant cells by the carcinogen, results in increased tumor growth and suppression of apoptosis, whose role is to reduce cancer incidence,” explained Michael Karin, Ph.D., UCSD professor of pharmacology and American Cancer Society Research Professor. "Our studies show how NF-kB acts very early in the carcinogenesis process, in two different ways.”

The authors stated that "Our findings establish for the first time the role of myeloid cells in inflammation-associated tumor promotion in addition to their role in tumor progression and invasiveness.” They also noted that the inhibition of IKK beta may be very effective in the prevention of colitis-associated cancer.




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