Objective
The entire intestinal epithelium is renewed every week due to cell division in the crypts coupled with cell migration towards the villi and loss of cells by apoptosis at the tip of villi. Uncoupling cell proliferation from apoptosis and possibly from cell migration can lead to pathologies such as cancer. In carcinoma in situ, the basement membrane (BM) represents a physical barrier that prevents spreading of the primary tumor to adjacent tissues. It is believed that cancer cells perforate BM, but stromal cells such as carcinoma-associated fibroblasts (CAFs) also secrete matrix proteinases. Thus, the question is who is invading whom – do cancer cells invade the stroma or is the stroma invading tumor cells?
Here we propose an innovative multi-disciplinary approach, at the interface of cancer cell biology and physics, combined with recent advances in optics aimed to unravel the fundamental mechanisms of cell migration in 3D environments during intestinal homeostasis and tumor invasion. Our specific aims are:
1. Determine the mechanism of epithelial cell migration in gut homeostasis. Using intestinal slice cultures and two-photon microscopy we will determine if epithelial cells migrate using cellular protrusions, are pushed by dividing cells, or are transported by underlying fibroblasts and BM.
2. Examine if cancer cells and CAFs cooperate to break the BM. We will use a 3D in vitro model to determine which cell type is degrading BM and if distinct sub-populations of CAFs have different functions.
3. Explore how cancer cells and CAFs cooperate during invasion of the stroma. 3D chemoattraction assays will be used to determine if CAFs can guide cancer cells towards blood vessels.
4. Characterize cooperation of cancer cells and CAFs in vivo. Using intravital imaging we will analyze interactions between cancer cells and CAFs in the primary tumor. Ortotopic mouse models will be used to determine if a specific sub-population of CAFs can trigger metastasis of colon cancer.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences cell biology
- natural sciences physical sciences optics microscopy
- medical and health sciences clinical medicine oncology colorectal cancer
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2012-StG_20111109
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
75231 Paris
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.