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Content archived on 2024-05-29

The role of semaphorins and neuropilins in tumour angiogenesis

Objective

Very little is known about receptor family of plexins, neuropilins and their ligands the semaphorins, in cancer progression and neo-angiogenesis. There are over 20 different semaphorins and nine plexins that can interact with each other in various ways. This scenario implicates a complex signalling pattern, the evaluation of which has only begun. It has recently been suggested that semaphorins possess both attractory and repulsory effects, which most likely are mediated by specific adaptor molecules and receptor tyrosine kinases (RTKs). The evaluation of the inhibitory, as well as promoting, function of different semaphorins, neuropilins and plexins is of great importance, and may lay the framework for therapeutic applications of these molecules.

This project is aimed at understanding the functional role and mechanisms whereby semaphorin and neuropilin signalling may regulate angiogenesis in pathological conditions, such as cancer progression with a specific focus on the down-steam signalling of the two receptors neuropilin 1 and 2. More specifically, the project will employ the highly effective lentiviral mediated gene transduction, as well as the novel technology based on haematopoietic bone marrow cells (TEMs) (De Palma 2003 and 2005). TEM cells will be transduced with the semaphoring/plexin/neuropilin of interest, which will then be injected into lethally irradiated mice, to allow for full engraftment of transplanted cells.

By these means, the aim is to obtain chimeric animals bearing a bone marrow-derived cell population able to selectively target the expression of a tumour-arresting molecule into the tumour vasculature. We will also be able to use semaphoring and neuropilin knock-out mouse models for tumour studies in collaboration with Prof. Christer Betsholtz of the Karolinska Institut, Stockholm, Sweden and Prof. Anne Eichmann of the Collegé de France, Paris, France.

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Keywords

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-11
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Funding Scheme

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EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

UPPSALA UNIVERSITY
EU contribution
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Total cost

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