Supervisor: Dr. Ingrid Langer
Tumours 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 tumour and the stromal cells give rise to a new pathological entity that evolves continuously during the progression of cancer: the tumour microenvironment or TME. The TME influences many aspects of tumorigenesis (growth, survival, migration and invasion of tumour cells, epithelial-mesenchymal transition, angiogenesis…) and the development of more aggressive tumours resistant to current therapies (1).
VIP is a neuropeptide that exerts pleiotropic effects in the body. VIP and its receptors are very interesting targets for both colorectal tumour imaging and targeted therapy. Indeed, these receptors are overexpressed in many cancers, including CRCs, and some studies have shown a correlation between their level of expression and the severity of tumours. While several studies have demonstrated the involvement of the VIP in tumorigenesis, these have focused mainly on studying the effects of VIP on cancer epithelial cells (2). The main objective of the project is to study the role of the VIP pathway in the tumour microenvironment of colorectal cancers. More precisely, we will evaluate the effects of VIP on fibroblasts as well as the interactions between cancerous epithelial cells and these stromal cells. All together, we expect that our results will help better understanding of the role of VIP and its receptors in the tumour microenvironment but also some aspects of the biology of colorectal tumours, with the ultimate goal of potentially developing new diagnostics and therapeutics.
References
1. Friend or foe? The tumour microenvironment dilemma in colorectal cancer. Colangelo T et al. Biochim Biophys Acta Rev Cancer. 2017 1867(1):1-18.
2. Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer. Moody TW et al. Curr Opin Endocrinol Diabetes Obes. 2016 23(1):38-47.8. Perez and Caspi, Immune mechanisms in inflammation and degenerative eye diseases. Trends Immunol. (2015) 36(6)354