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The dual effects of a novel peptibody on angiogenesis inhibition and M2 macrophage polarization on sarcoma
- Source :
- Cancer letters. 416
- Publication Year :
- 2017
-
Abstract
- Inhibition of the VEGF/VEGF receptor (VEGFR) and angiopoietin-2 (Ang-2)/TEK receptor tyrosine kinase (Tie-2) pathway is a potential target for tumor angiogenesis. We previously showed that a peptide AS16 which dually inhibits VEGFR/Ang-2 could reduce the tumor growth and decrease the number of microvessels in tumor. However, its short circulating half-life in the serum limits its clinical applications. In this study, as an effort to prolong the short in vivo half-life of AS16, we designed a fusion protein containing peptide AS16 and an IgG Fc fragment. Pharmacokinetic study also revealed that AS16-Fc has a prolonged circulating half-life of about 231 min in rats. We examined the effects of treatment on the tumor vasculature and immune cell populations, tumor growth, in both the MCA-205 and S180 tumor models. We found that AS16-Fc dramatically reduced tumor volume, vascular density and tumor-associated macrophages. Macrophages were identified as potential novel targets following anti-angiogenic therapy, our findings imply a novel role for anti-angiogenic peptide AS16-Fc. These findings indicate that AS16-Fc could be more effective on inhibiting tumor growth angiogenesis and tumor immune microenvironment than that of peptide AS16.
- Subjects :
- 0301 basic medicine
Cancer Research
Immunoconjugates
Angiogenesis
Macrophage polarization
Angiogenesis Inhibitors
Rats, Sprague-Dawley
03 medical and health sciences
Mice
Immune system
Cell Line, Tumor
Tumor Microenvironment
Animals
Humans
Tumor microenvironment
biology
Neovascularization, Pathologic
Chemistry
Macrophages
Macrophage Activation
M2 Macrophage
Fusion protein
Angiopoietin receptor
Immunoglobulin Fc Fragments
030104 developmental biology
Oncology
Immunoglobulin G
Cancer research
biology.protein
Female
Sarcoma, Experimental
Peptides
Tyrosine kinase
Subjects
Details
- ISSN :
- 18727980
- Volume :
- 416
- Database :
- OpenAIRE
- Journal :
- Cancer letters
- Accession number :
- edsair.doi.dedup.....c8b99e0935d17a256e317844634c97dc