Ricerc@Sapienza

Colorectal cancer (CRC) is one of the most common cancer and leading cause of death worldwide. In the last decades, a tight connection between CRC development and intestinal chronic inflammatory state has been established. Indeed, patients affected by inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn¿s disease (CD), show an increased risk of developing colon cancer. Recently, specific cell types have been reported to substantially contributeto these inflammatory states. Enteric glial cells (EGCs) are cellular population composing enteric nervous system (ENS) distributed in submucosal and mioenteric plexi located along the intestinal wall and display a pivotal role in the sustaining and perpetuation of inflammatory conditions, due to their capability to induce immune-inflammatory responses following detrimental noxia, through the release of pro-inflammatory cytokines and factors, such as S100B, NO and IL-1ß. The putative involvement of EGCs in CRC onset has been hypothesized and the possible targeting of EGCs may represents an innovative strategy in the prevention of inflammation-related CRC. In this context, palmitoylethanolamide (PEA) may be an intriguing compound able to prevent the neoplastic drift from a long-standing inflammation through its well-known capability to modulate EGCs activation added to its anti-angiogenic activity in vitro. PEA efficacy has been already demonstrated in a murine model of colitis, but its putative role as drug able to reduce CRC risk have not investigated yet. To this aim the present study will evaluate, in a murine model of colitis-associated colon cancer, the role exerted by EGCs in neoplastic processes from chronic inflammation and the preventive effect of PEA in colon cancer outbreak. Data obtained will be useful to better understand the cellular mechanisms promoting carcinogenic processes and to identify a promising approach in the prevention of intestinal chronic inflammation-associated colon cancer.