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Deciphering and targeting the molecular mechanisms that drive the mechanically-induced cancer metastasis to bones.

Project description

Insight into the role of mechanical forces in cancer metastasis

Cancer development is a complex and multistep process where genetic mutations lead to deregulated cell growth and proliferation. An increasing body of evidence suggests that the tissue microenvironment also plays a key role in tumour initiation and progression. Growing tumours receive mechanical forces from the surrounding tissues, which causes solid stress and triggers metastasis. Migrating cancer cells are also exposed to shear forces caused by blood flow. The scope of the EU-funded MECHANiCM project is to understand how solid stress and shear forces influence the metastatic potential of cancer cells. Through a multidisciplinary approach, researchers will dissect the molecular mechanisms of metastasis and identify potential targets for therapeutic intervention.

Objective

Mechanical abnormalities of the tumor microenvironment (TME) have gained much attention over the last decades as potent drivers of tumor progression. These abnormalities include compressive forces that generate the so-called solid stress. Solid stress is suggested to affect the metastatic potential of several tumor types, including breast cancer, however the exact molecular mechanisms involved remain to be explored. Once cancer cells have left the primary tumor site and entered into the blood stream are also exposed to shear stress exerted by blood flow. Shear stress is considered to be lower during flow, and higher during intravascular arrest. The arrested cancer cells must develop mechanisms of adhesion to efficiently resist such forces for successful extravasation, however the involved mechanisms are elusive. In particular, the third most common secondary tumor site for breast cancer is bone. There, cancer cells interact with bone-specific cells, that are also exposed to shear forces due to blood flow in the bone environment. To this end, the applicant proposes to test the hypothesis that the presence of solid stress in TME, and shear stress in the blood stream are important physical parameters that could trigger cancer cell metastasis. Therefore, it is highly value to identify the molecular mechanisms involved to target and reverse the metastatic process. The proposed research combines knowledge in the fields of bone and cancer biology and mechano-pathology, bioengineering and biophysics, and cutting-edge techniques. A pharmaceutical screening will be also performed in vitro and in vivo to suggest possible therapeutic interventions to prevent breast cancer metastasis. In the proposed project, the fellow will acquire scientific and complementary skills according to her personalized career development plan, while through advanced training and inter-sectoral mobility she will reach a position of professional maturity in research.

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

LINKOPINGS UNIVERSITET
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.

€ 203 852,16
Address
CAMPUS VALLA
581 83 Linkoping
Sweden

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Region
Östra Sverige Östra Mellansverige Östergötlands län
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.

€ 203 852,16
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