Cancer progression is a complex process where cells acquire aberrant proliferative, survival and migratory properties, as well as the ability to trigger the formation of a dedicated tumour blood supply. There is now compelling evidence that the bulk of the malignant cells in cancers contained a rare fraction of self-renewing, multi-potent, and tumour-initiating cells, termed stem-like cancer cells (SLCCs), that constitute a reservoir to generate and/or maintain the tumours. Such as developmental or normal stem cells, cancer stem cells reside within a stem cell niche, which heterogeneous composition always contains a vascular structure. Therefore, in addition to the delivery of nutrients and oxygen, and to provide a circulating option for metastatic cells, the tumour blood vessels may also form a specific and confined microenvironment where endothelial cells from the vascular wall and tumour stem cells from the tumour mass may interact. Indeed, these SLCCs reside in close proximity of tumour blood. In line with these recent observations and hypothesis, we propose to explore the nature of the interactions between “cancer” stem cells and brain endothelium, and how this niche may impact both stemness properties and endothelial barrier function. My research program involved 3 major aims:
- Influence of the endothelium/cancer stem cell interactions on their transcriptome
- Modulation of mTor signalling axis in the tumour vascular niche
- Semaphorin signalling in the vascular niche
Through the combination of innovative technologies and approaches, such as transcriptome analysis, cell imagery, in vivo model of angiogenesis, we have here a unique opportunity to better understand the basis for molecular and cellular interactions within the tumour microenvironment. Overall, I expect my proposal research to provide the molecular basis for the development of novel therapeutic targets designed to impede on deregulation of the vascular niche or to promote its normalization.
Fields of science
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