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Role of Mitochondrial Physiology in Tumor Stem Cell Resistance to Chemotherapeutics (MitoCancerStem)
Date du début: 1 août 2010, Date de fin: 31 juil. 2012 PROJET  TERMINÉ 

Although many advances in cancer research have heightened cases of long term survival, tumor re-growth is still a major concern. One hypothesis of the driving force behind tumor re-growth is the subpopulation of cancer stem cells found in varying types of tumors. Cancer stem cells have emerged as an important chemotherapeutic target over the past decade, as their ability to evade treatments provides a likely source for tumor re-growth. Like organs, tumors are composed of a mixture of cells at varying states of differentiation and arise from cells with the ability to proliferate indefinitely and differentiate into multiple lineages. In healthy organs, the cells responsible for organ development are stem cells, suggesting that tumors also have a subset of cells with stem-like characteristics known as cancer stem cells. Over the past decade, support for the existence of cancer stem cells has grown, suggesting that cancer stem cells are a driving force in tumorigenesis.This project is devised to investigate mitochondrial characteristics of cancer stem cells that allow them to survive the effects of chemotherapeutic drugs, especially those targeting apoptotic pathways. Our working hypothesis will be that the differential physiology of mitochondria in tumor stem cells and differentiated cells result into a different susceptibility to chemotherapeutics.To pursue the objective of the present work we will use mouse P19 embryonal carcinoma cells (TSC), which are a unique system on the basis that cancer stem cells can be compared with more differentiated cancer tumor cells in the same cell line under two different conditions. Preliminary data from the host group clearly demonstrates that mitochondrial differentiation accompanies cell differentiation. The consequences for cell metabolism and resistance to pro-oxidants, chemotherapeutics and mitochondrial inhibitors of the different mitochondrial subtypes are not known and constitute the basis of this proposal.

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