Linking chronic inflammation leads to cancer.

It is well known that several types of cancer occur in the setting of chronic inflammation.  For example, patients with ulcerative colitis and Crohn's Disease are at high risk to develop colorectal cancer.  The laboratory has proposed that PACAP, which is expressed in intestinal neurons, acts in the intestinal mucosa microenvironment to regulate immune tolerance and to protect against excess inflammation. To determine if this is the case, they subjected PACAP-deficient mice to a well established mouse model for ulcerative colitis (Int J Cancer 2008). Compared to wild type controls, PACAP-deficient mice were found to exhibit much more severe colitis and a higher degree of inflammation [Fig. 1 and Fig. 2].  Moreover, in the two month trial period, 60% of the PACAP-deficient mice developed aggressive colorectal tumors, whereas none of the wild type mice developed such tumors [Fig. 4]. In addition to providing a mouse model which rapidly develops inflammation-associated colorectal cancer without the use of a carcinogen, the studies strongly suggest that endogenous PACAP protects mice from inflammation and inflammation-associated colorectal cancer.