Cancer Stem Cell Fate and Polarity Control by Stroma Viscoelastic Properties
Project acronym: CAPOSTROMEX
Topics: cancer stem cells, epithelial breast tumor, stroma physical properties, polarity genes, molecular pathways
Disciplinary fields : cancerology, cell biology, biophysics, microscopy
Summary: It is known that stroma of solid tumor is typically stiffer than normal, which is the root of basic physical tumor detection. Recently, a stiffer tumor microenvironment has been linked to tumor progression, yet a relationship betweenepithelial tumor heterogeneity and stroma local physical properties have not been established. This interdisciplinary project aims, at first, describing the relationship between epithelial breast tumor heterogeneity, cancer stem cell (CSC) behavior and stroma physical properties in patients by state of the art physical and imaging technologies to provide models to be tested in vivo (PDX and tumors in mouse) and in vitro (in tumoroids and tumors cells). The first proposition is to manipulate the rigidity of the stroma matrix locally or globally. Then, an evaluation of the impact of such variations on tumor growth, dissemination and migration and on CSC gene expression profile will be done, in order to refine the models. Finally, the models will be implemented by manipulating the expression of polarity genes (apico-basal and planar polarity) and newly identified genes from CSC reacting to stroma physical changes to define molecular pathways that impact tumor growth and dissemination.
Project duration: 04/01/2018 – 03/31/2021
Call for application: Interdisciplinarité 2016