The role of the VIP/VPAC1 pathway in the tumor microenvironment of colorectal cancers

Supervisor: Dr. Ingrid Langer

Tumors are now recognized as a complex tissue composed of multiple distinct cell types mainly derived from the surrounding mesenchymal stroma (stromal cells, leukocytes, extracellular matrix). Functional interactions between the tumor and the stromal cells give rise to a new pathological entity that evolves continuously during the progression of cancer: the tumor microenvironment or TME. The TME influences many aspects of tumorigenesis (growth, survival, migration and invasion of tumor cells, epithelio-mesenchymal transition, angiogenesis, …) and the development of more aggressive tumors resistant to current therapies.

VIP is a neuropeptide that exerts through its receptor VPAC1, pleiotropic effects in the body. VPAC1 is a very interesting target for both colorectal tumor imaging and targeted therapy. Indeed, these receptors are overexpressed in many cancers, including CRC, and some studies have shown a correlation between their level of expression and the severity of tumors. While many studies have demonstrated the involvement of the VIP /VPAC1 pathway in tumorigenesis, these have focused primarily on studying the effects of VIP on cancer epithelial cells.

The main objective of our project is to study the role of the VIP/VPAC1 pathway in the tumor microenvironment of colorectal cancers. Specifically, we will evaluate the effects of VIP on TME fibroblasts and macrophages as well as the interactions between cancerous epithelial cells and these stromal cells.

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