Breast cancer and tumoral exosomes involved in cognitive disorders associated with cancer? Proof of concept study
Coordinator: Hélène Castel (Rouen)
To date, no reliable biological data in patients and animal models allow to understand how cancer itself can impact brain function at short and long term. Plasma factors released by the tumor itself would be vectors of brain function modifications. Among the potential plasma factors, we hypothesize that circulating proteins and micro-RNAs (Mir) contained and released by exosomes evolving from certain cancers, and in particular breast cancer, can directly or indirectly impact the central nervous system. This pioneer project is starting as a “proof of concept”, and is currently unique on the national and international level, in its design.
The project will consist in establishing the impact of cancer and especially exosomes released by human and murine mammary tumors and the different contents of proteins and Mir on neural cells, brain plasticity and mouse behavior.
Thus, plasma or murine or human mammary xenografted cancer exosomes will be injected into non-tumor-bearing mice for evaluation of emotion and cognitive functions as well as brain plasticity. A strategy will be put in place to evaluate the potential passage of these exosomes in vivo through the blood-brain barrier, and exosomes from serum of xenografted animals will be tested in cultures on human neural stem cells, astrocytes, neurons and endothelial cells to evaluate the direct impact of tumoral exosomes on cell viability and differentiation.
Nadira Delhem (OncoThai) and Michel Salzet (PRISM) Lille
Inserm, Normandie Rouen University, “projet Emergent” CNO.