Mast cells (MCs) are tissue resident sentinels that orchestrate inflammation in response to infection and allergens. They are also frequently observed in tumors, suggesting their contribution in the transition from persistence inflammation to carcinoma. However, the exact role of MCs in tumorigenesis remains controversial: MC-derived mediators can either exert pro-tumorigenic functions, causing progression and spread of the tumor, or anti-tumorigenic functions, limiting tumor growth.
Particularly, there have been a considerable number of contradictory observations regarding the detrimental or protective roles of MCs in colorectal carcinoma (CRC) development, and the relationship between MCs, tumor progression and clinical outcome in patients with CRC have remained largely unclear. Due to the complexity of CRC pathogenesis, the identification of is a pressing unmet need. Consequently, a more comprehensive understanding of MC contribution in each stage of the disease is highly needed to unveil novel mechanisms underlying CRC pathogenesis and to identify new molecular players implicated in the loss integrity of the gut epithelial barrier.
Overall, this proposal aims at evaluating the role of MCs in CRC development and at identifying the main molecular pathways able to tune MC plasticity during tumor progression with the purpose to identify novel markers of distinct MC subsets and/or disease progression.