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Pericyte-derived tumor stroma – a target for cancer therapy

Objective

Cancer is a devastating diagnosis since treatments to prevent a lethal outcome are limited. Tumor constitutes a complex tissue consisting of malignant cells and stromal cells. Emerging studies have shown the importance of stroma in tumor growth, invasion, and metastasis highlighting its potential as an attractive target for cancer therapy. However, the source of tumor stroma generating cells remains elusive. Generation of connective tissue is a general feature of scarring and fibrosis. While scarring is part of the wound healing response, fibrosis represents a failure to terminate tissue repair. In this context, tumors can be considered as “wounds that do not heal”. While studying spinal cord injury-induced scarring, a subpopulation of perivascular cells, type A pericytes, has been shown to be a major source of the stromal scar. Type A pericytes are embedded in the vascular wall but proliferate and leave blood vessels upon injury, differentiating into fibroblast-like cells that deposit extracellular matrix and form the stromal scar. Here, I propose to determine whether type A pericytes are a source of tumor stroma and whether blocking type A pericyte-derived stroma formation can impede cancer progression. Single cell studies to determine pericyte heterogeneity within malignant and non-malignant tissue will be performed. This characterization of heterogeneity is important to distinguish stroma-forming pericytes from the non-forming ones and from tumor cell-derived pericytes as described in Glioblastoma multiforme (GBM). Furthermore, by using combinations of pericyte reporter mice with genetic tools to manipulate pathways regulating cell proliferation and recruitment within specific pericyte subpopulations, I aim to investigate underlying mechanisms mediating pericyte-derived stroma generation. Studying stroma formation using the GBM mouse model, the proposed research intends to uncover common mechanisms of tumor stroma formation and identify new targets for therapy.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

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-2015

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Coordinator

KAROLINSKA INSTITUTET
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.

€ 185 857,20
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms 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.

€ 185 857,20
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