Inflammation and CRC: Necroptosis and Fibroblasts Tip the Balance
Abstract
Inflammation is known to promote and fuel the progression of CRC. However, the causes that trigger such inflammation and the cells that mediate tumor-promoting inflammation remain unknown. We propose that damage and inflammation is not uncommon in the gut, but that the types of inflammation in the intestine are distinct. Specifically, CRC-promoting inflammation is categorically different, and we propose that inflammation of a non-immune cell known as fibroblast underlies the etiology of CRC. We also posit that a very specific form of cellular damage - the death of intestinal epithelial cell by a molecular program called necroptosis drives inflammation of fibroblasts. Thus, the scientific objective of the research project we propose is to characterize fibroblast inflammation and immune cell inflammation under conditions wherein intestinal epithelial cells die by necroptosis in mouse models of CRC, including new models developed in our laboratory. This will help determine if this specific type of damage and resulting inflammation is preferentially associated with and causes CRC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2023
- Accession Number
- AD1217443
Entities
People
- Carla V. Rothlin
Organizations
- Yale University