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- W2315440152 abstract "Basement membrane represents a physiological barrier between epithelial tissues and their microenvironment. In invasive carcinomas, the membrane is breached and cancer cells disseminate in the stroma. In this PhD thesis, I investigated how cancer cells breach the BM and whether a stromal cell population, fibroblasts, assist them in that process. I used colorectal cancer as a model. In collaboration with the Institut Curie Hospital, we isolated human primary fibroblasts from human colorectal cancers, called CAFs and the adjacent normal tissue, NAFs. To study BM invasion, I developed a 3D in vitro assay based on the mouse mesentery. We showed that CAFs, and rarely NAFs, induce cancer cell invasion. This pro-invasive effect is mainly mediated when CAFs are physically present on the membrane, rather than through paracrine ways. To understand how CAFs facilitate invasion, we performed a proteomic comparison between cancer cell-stimulated CAFs and NAFs. Results showed that CAFs produced more proteins-components of the ECM, matrix remodelers and they were more contractile compared to NAFs. Further, we wished to understand the mechanism by which CAFs mediate their effect. We showed that CAFs can induce invasion in a MMP independent way. However, Inhibition of contractility abolished CAFs capacity to induce invasion. Dynamic analysis of cancer cells-fibroblasts co-cultures showed that CAFs could pull on the BM fibers. To directly test this possibility, we created holes in the BM using laser ablations. While in the presence of cancer cells alone, holes remained the same size, in the presence of CAFs, holes widen over time. We further showed that this mechanism is MMP independent but depends on contractility. Altogether, these results demonstrate that CAFs stimulate cancer cell invasion through BM by acting directly on the BM, possibly by depositing ECM components and proteins that remodel ECM and by exerting physical forces on the membrane by contraction." @default.
- W2315440152 created "2016-06-24" @default.
- W2315440152 creator A5060813359 @default.
- W2315440152 date "2015-09-21" @default.
- W2315440152 modified "2023-09-24" @default.
- W2315440152 title "Le rôle des fibroblastes associés aux carcinomes dans l’invasion de la membrane basale par les cellules cancéreuses" @default.
- W2315440152 hasPublicationYear "2015" @default.
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