Therapeutic efficacy of a synthetic epsin mimetic peptide in glioma tumor model: uncovering multiple mechanisms beyond the VEGF-associated tumor angiogenesis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-05

AUTHORS

Jerry Dong, Debra Saunders, Robert Silasi-Mansat, Lili Yu, Hua Zhu, Florea Lupu, Rheal Towner, Yunzhou Dong, Hong Chen

ABSTRACT

Binding of epsin ubiquitin-interacting motif (UIM) with ubiquitylated VEGFR2 is a critical mechanism for epsin-dependent VEGFR2 endocytosis and physiological angiogenesis. Deletion of epsins in vessel endothelium produces uncontrolled tumor angiogenesis and retards tumor growth in animal models. The aim of this study is to test the therapeutic efficacy and targeting specificity of a chemically-synthesized peptide, UPI, which compete for epsin binding sites in VEGFR2 and potentially inhibits Epsin-VEGFR2 interaction in vivo, in an attempt to reproduce an epsin-deficient phenotype in tumor angiogenesis. Our data show that UPI treatment significantly inhibits and shrinks tumor growth in GL261 glioma tumor model. UPI peptide specifically targets VEGFR2 signaling pathway revealed by genetic and biochemical approaches. Furthermore, we demonstrated that UPI peptide treatment caused serious thrombosis in tumor vessels and damages tumor cells after a long-term UPI peptide administration. Besides, we revealed that UPI peptides were unexpectedly targeted cancer cells and induced apoptosis. We conclude that UPI peptide is a potent inhibitor to glioma tumor growth through specific targeting of VEGFR2 signaling in the tumor vasculature and cancer cells, which may offer a potentially novel treatment for cancer patients who are resistant to current anti-VEGF therapies. More... »

PAGES

17-27

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11060-018-2766-z

DOI

http://dx.doi.org/10.1007/s11060-018-2766-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100559215

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29357089


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Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s11060-018-2766-z'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s11060-018-2766-z'


 

This table displays all metadata directly associated to this object as RDF triples.

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