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Modulating the behaviour of cancer myofibroblasts to control tumour desmoplasia

Objective

In many tumors a desmoplastic reaction takes place during progression, which results in extensive production of collagen by stromal cells of the tumor, mainly fibroblasts and myofibroblasts. Tumor desmoplasia determines in large part the patho-physiology of solid tumors and poses a major barrier to effective drug delivery, affecting the overall survival of cancer patients. Here, the applicant proposes to test the hypothesis that the increase in extracellular matrix (ECM) stiffness and transforming growth factor-beta (TGFβ) activation often observed during tumor progression have additive effects on tumor desmoplasia. Therefore, targeting any of these parameters alone or in combination can reduce the desmoplastic response of the stromal cells. To explore this hypothesis, a combination of cutting-edge techniques will be employed. Specifically, a collagen ECM model, with pre-determined topography and tunable stiffness will be developed. Subsequently, fibroblasts and myofibroblasts will be cultured in the ECM models. Cells nano-mechanical behavior and their morphodynamic alterations will be investigated with Atomic Force Microscopy and light/fluorescence microscopy under the presence or absence of TGFβ or anti-TGFβ agents. Finally, the effects of matrix stiffness along with different TGFβ concentrations in the expression pattern of genes encoding ECM components will be investigated using real-time PCR. The research results will elucidate the mechanisms of the interplay between matrix stiffness and TGFβ production in modulating the ability of fibroblasts and myofibroblasts to form tumor desmoplasia. In the proposed project, the fellow will acquire scientific and complementary skills according to his personalized career development plan and through advanced training, international and inter-sectoral mobility will reach a position of professional maturity in research.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

UNIVERSITY OF CYPRUS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 163 648,80
Address
AVENUE PANEPISTIMIOU 2109 AGLANTZI
1678 Nicosia
Cyprus

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Region
Κύπρος Κύπρος Κύπρος
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 163 648,80
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