Effect of mutant Endostatin and Kringle 5 fusion protein on Tumor angiogenesis.
2016-05
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
Effect of mutant Endostatin and Kringle 5 fusion protein on Tumor angiogenesis.
Authors
Published Date
2016-05
Publisher
Type
Thesis or Dissertation
Abstract
Angiogenesis is important for the growth and metastasis of tumors. Endostatin is an endogenous inhibitor of angiogenesis and is shown to inhibit bFGF and VEGF induced signaling in endothelial cells. Recent evidence also indicates that it binds to αν and α5 group of integrins expressed endothelial cells and inhibits downstream signaling. Kringle 5, a potent anti-angiogenic molecule causes apoptosis of endothelial cells by associating with glucose-regulated protein 78 (GRP78). Previous studies from our laboratory have shown that a mutant (P125A) form of Endostatin (derived from collagen type XVIII) and Kringle 5 fragment of plasminogen can inhibit angiogenesis by inducing autophagy. P125A-endostatin and Kringle 5 interfere with distinct signaling pathways in endothelial cells. We hypothesized that a chimeric protein made of P125A-endostatin and Kringle 5 will have better anti-angiogenic activities. To test this hypothesis, we constructed a fusion protein consisting of P125A-endostatin and Kringle 5 (E-K5). Recombinant fusion protein was expressed in yeast and purified. E-K5 was found to inhibit proliferating endothelial cells and effectively blocked tumor induced angiogenesis. Anti-proliferative activity of E-K5 was linked to VEGF receptor and ανβ3 integrin-mediated signaling pathways. These studies establish the therapeutic potential of E-K5 as a potent anti-angiogenic molecule.
Description
University of Minnesota M.S. thesis. 2016. Major: Pharmacology. Advisor: Sundaram Ramakrishnan. 1 computer file (PDF); 60 pages.
Related to
Replaces
License
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Suggested citation
Venkatachalam, Annapoorna. (2016). Effect of mutant Endostatin and Kringle 5 fusion protein on Tumor angiogenesis.. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/181823.
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.