PTPS IN ANGIOGENESIS · Role of protein-tyrosine phosphatases in angiogenesis
FP7 — People (Marie Curie Actions)
- Duration
- 2009-07-01 → 2011-06-30
- EU contribution
- €180,801
- Participants
- 1
- Scheme
- MC-IEF
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Results in brief
Role of protein-tyrosine phosphatases in angiogenesis
It is estimated that more than 500 million people will benefit from anti- or pro-angiogenesis treatments in the coming decades. Angiogenesis is the formation of new blood vessels from pre-existing ones and is involved in different physiological and pathological processes. Tyrosine phosphorylation is a reversible process, mediated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) that regulate critical cell signalling pathways. Both PTKs and PTPs play a vital regulatory role in many important biological processes including proliferation, migration, differentiation, and apoptosis and their deregulation can lead to diseases such as cancer. Although the role of several PTKs in angiogenesis is well studied, little is known about the role of specific PTPs in this process. Our goals were to determine the biological roles of specific PTPs in endothelial cells in vitro and in vivo. We assessed the expression of specific PTPs in endothelial cells, developed shRNA systems to knockdown PTPs and tested the effect of knockdown of PTP?, PTPN14 and PTP1B in a 3D in vitro spheroid assay as well as using in vivo assays. We found no significant effect of knockdown of these PTPs in these assays suggesting a level of redundancy among PTPs in angiogenesis and a need for knocking more than one PTP in ECs.
Data: CORDIS, © European Union
Project objective
Angiogenesis is the formation of new blood vessels from pre-existing ones and is involved in different physiological and pathological processes such as cancer and ischemia. Tyrosine phosphorylation is a reversible process, mediated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). Although the role of PTKs in angiogenesis is well established, little is known about the function of specific PTPs in this process. In collaboration with Dr. H. Augustin, (Heidelberg, Germany) we found that the expression of several PTPs changes when spheroids of endothelial cells embedded in 3D matrices are exposed to angiogenic stimuli. To investigate the role of PTPs in angiogenesis, we generated a tetracycline-inducible shRNA library for targeting PTPs. We are also generating lentiviral vectors expressing inducible cDNAs of all the human PTPs. I propose to investigate the biological role of PTPs in angiogenesis by loss- and gain of function experiments in endothelial cells, using different in vitro and in vivo angiogenesis assays. My studies will determine the role of PTPs in developmental and pathological angiogenesis and test their merits as targets of angiogenic therapy.
Original text from CORDIS.
Participants
- Novartis Forschungsstiftung · BASELCoordinatorCity levelSwitzerland
Links
Data: CORDIS, © European Union