Increased blood vessel density and endothelial cell proliferation in multiple sclerosis cerebral white matter

Vascular endothelial protein tyrosine phosphatase (VE-PTP) is an endothelial-specific receptor-type tyrosine phosphatase that associates with Tie-2 and VE-cadherin. VE-PTP gene disruption leads to embryonic lethality, vascular remodeling defects, and enlargement of vascular structures in extraembryonic tissues. We show here that antibodies against the extracellular part of VE-PTP mimic the effects of VE-PTP gene disruption exemplified by vessel enlargement in allantois explants. These effects require the presence of the angiopoietin receptor Tie-2. Analyzing the mechanism we found that anti–VE-PTP antibodies trigger endocytosis and selectively affect Tie-2–associated, but not VE-cadherin–associated VE-PTP. Dissociation of VE-PTP triggers the activation of Tie-2, leading to enhanced endothelial cell proliferation and enlargement of vascular structures through activation of Erk1/2. Importantly, the antibody effect on vessel enlargement is also observed in newborn mice. We conclude that VE-PTP is required to balance Tie-2 activity and endothelial cell proliferation, thereby controlling blood vessel development and vessel size.

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Faculty Opinions recommendation of HLA class I molecules partner with integrin β4 to stimulate endothelial cell proliferation and migration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7711957.8463067 ◽

2011 ◽

Author(s):

Arthur Mercurio

Keyword(s):

Cell Proliferation ◽

Endothelial Cell ◽

Hla Class I ◽

Class I ◽

Endothelial Cell Proliferation ◽

Cell Proliferation And Migration ◽

Hla Class I Molecules ◽

Integrin Β4 ◽

And Migration ◽

Proliferation And Migration

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Bioinformatics-based approach for identifying peptide inhibitors of endothelial cell proliferation and migration

Science-Business eXchange ◽

10.1038/scibx.2008.788 ◽

2008 ◽

Vol 1 (32) ◽

pp. 788-788

Keyword(s):

Cell Proliferation ◽

Endothelial Cell ◽

Peptide Inhibitors ◽

Endothelial Cell Proliferation ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

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Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression

Angiogenesis ◽

10.1007/s10456-021-09776-8 ◽

2021 ◽

Author(s):

Delphine M. Lees ◽

Louise E. Reynolds ◽

Ana Rita Pedrosa ◽

Marina Roy-Luzarraga ◽

Kairbaan M. Hodivala-Dilke

Keyword(s):

Blood Vessel ◽

Tumour Growth ◽

Vascular Endothelial Cell ◽

Vessel Density ◽

In Vivo Studies ◽

Blood Vessel Density ◽

Tumour Vessel ◽

Vessel Regression ◽

Tumour Blood

AbstractFocal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is overexpressed in many cancer types and in vivo studies have shown that vascular endothelial cell FAK expression and FAK-phosphorylation at tyrosine (Y) 397, and subsequently FAK-Y861, are important in tumour angiogenesis. Pericytes also play a vital role in regulating tumour blood vessel stabilisation, but the specific involvement of pericyte FAK-Y397 and FAK-Y861 phosphorylation in tumour blood vessels is unknown. Using PdgfrβCre + ;FAKWT/WT, PdgfrβCre + ;FAKY397F/Y397F and PdgfrβCre + ;FAKY861F/Y861F mice, our data demonstrate that tumour growth, tumour blood vessel density, blood vessel perfusion and pericyte coverage were affected only in late stage tumours in PdgfrβCre + ;FAKY861F/Y861F but not PdgfrβCre + ;FAKY397F/Y397F mice. Further examination indicates a dual role for pericyte FAK-Y861 phosphorylation in the regulation of tumour vessel regression and also in the control of pericyte derived signals that influence apoptosis in cancer cells. Overall this study identifies the role of pericyte FAK-Y861 in the regulation of tumour vessel regression and tumour growth control and that non-phosphorylatable FAK-Y861F in pericytes reduces tumour growth and blood vessel density.

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