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Theses

L’enzyme CD10 : un acteur clé dans l’identification et la régulation des cellules souches mammaires humaines

Abstract : In breast, the existence of cancer stem cells has been demonstrated and that explain a number of observations as tumour heterogeneity. Other studies have demonstrated the resistance of radio and chemotherapy by different innate or acquired stem cell specific mechanisms that could explain relapse few years after the traitment. For all these reasons, that is very important to understand these mechanisms and to know physiological actors both implicated in the regulation of normal or cancer stem cells. CD10 is a zinc-dependant metallo-endopeptidase that inactivates a number of signalling peptides that could be implicated in mammary growth and differentiation. We have showed that CD10+ cell sorted population is enriched in Stem Cells/Early Common Progenitors/MyoEPithelial cells. We demonstrate that the protease activity of CD10 and the adhesion function of beta1-integrin are required to prevent differentiation of mammary stem cells/early progenitors. Taken together, our data suggest that integrin-mediated contact with the basement membrane and cleavage of signalling factors by CD10 are key elements in the microenvironment that maintains the progenitor and stem cell pools in the mammary gland. Adipose tissue is also a major component of the mammary microenvironment implicated in its homeostasis by the secretion of soluble factors. Our results suggested that the adipose tissue could be considered as a potential source of stem cells that differentiated into the luminal epithelial lineage involved in some breast cancers.
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Élodie Bachelard Cascales. L’enzyme CD10 : un acteur clé dans l’identification et la régulation des cellules souches mammaires humaines. Médecine humaine et pathologie. Université Claude Bernard - Lyon I, 2010. Français. ⟨NNT : 2010LYO10313⟩. ⟨tel-00703178⟩

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