Objective
Osteosarcoma (OS) is a very aggressive malignant bone tumor that develops primarily during childhood and adolescence. It is characterized by rapid growth, a strong tendency for recurrence and an extremely high metastatic potential. In the last three decades OS survival in the presence of metastasis has stagnated at a dismal 30%, clinical trials proved unsuccessful and no major breakthrough in the treatment of OS has been reported. To stop OS mortality, alternative therapeutical approaches urgently need to be explored.
Studies into the molecular and cellular events underlying OS revealed complex and heterogeneous genetic alterations, which challenge the prospect of finding and exploiting an unique molecular driver underlying OS. Because OS onset occurs at sites of rapid bone growth during the adolescent growth spurt, microenvironmental factors and tumor stroma may have a defining role in OS development and progression. Surprisingly, the intercellular cross-talk between OS cells and components of the tumor stroma, in particular mesenchymal stem cells (MSCs), have been poorly investigated.
Here I intend to demonstrate that tumor secreted vesicles called “exosomes” function as a key microenvironmental factor in OS progression by controlling tumor-stromal cells interactions. Specifically, we aim to explore whether MSC become pro-tumorigenic and pro-metastatic upon interaction with OS exosomes in bioluminescent mouse xenograft models. To identify the molecular signals (i.e. proteins and regulatory RNAs) in OS exosomes responsible for altering MSC behavior, we will employ state-of-the-art proteomics and deep-sequencing techniques. Finally, by means of functional assays we wish to discover the mechanisms by which OS exosome “educate” MSCs.
The identification of and interference with this completely unexplored layer of communication will lay the groundwork for novel therapeutical approaches to stop OS high mortality rate.
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
- medical and health sciences basic medicine immunology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pharmacology and pharmacy
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
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.
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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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.
1081 HV Amsterdam
Netherlands
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.