Abstract
Angiogenesis plays an essential role in rapid growing and metastasis of the tumors. Inhibition of angiogenesis is a putative strategy for cancer therapy. Endostatin (Es) is an attractive anti-angiogenesis protein with some clinical application challenges including; short half-life, instability in serum and requirement to high dosage. Therefore, production of recombinant endostatin (rEs) is necessary in large scale. The production of rEs is difficult because of its structural properties and is high-cost. Therefore, this review focused on the different expression systems that involved in rEs production including; mammalian, baculovirus, yeast, and Escherichia coli (E. coli) expression systems. The evaluating of the results of different expression systems declared that none of the mentioned systems can be considered to be generally superior to the other. Meanwhile with considering the advantages and disadvantage of E. coli expression system compared with other systems beside the molecular properties of Es, E. coli expression system can be a preferred expression system for expressing of the Es in large scale. Also, the molecular bioengineering and sustained release formulations that lead to improving of its stability and bioactivity will be discussed. Point mutation (P125A) of Es, addition of RGD moiety or an additional zinc biding site to N-terminal of Es , fusing of Es to anti-HER2 IgG or heavy-chain of IgG, and finally loading of the endostar by PLGA and PEG- PLGA nanoparticles and gold nano-shell particles are the effective bioengineering methods to overcome to clinical changes of endostatin.
Highlights
Angiogenesis is multi step formation of new blood vessel from the pre-existing ones and circulating endothelial precursors.[1]
With considering the advantages and disadvantage of E. coli expression system compared with other systems beside the molecular properties of Es, E. coli expression system can be a preferred expression system for expressing of the Es in large scale
Es is an attractive candidate as an anticancer protein that has been extensively studied for the cure of cancer, rheumatoid arthritis and retinopathies.[17]
Summary
The Challenges of Recombinant Endostatin in Clinical Application: Focus on the Different Expression Systems and Molecular Bioengineering. Abbas Mohajeri[1,2], Sarvin Sanaei[2], Farhad Kiafar[1], Amir Fattahi[3], Majid Khalili[4], Nosratollah Zarghami2,3,5* 1 Department of Biotechnology, Zahravi Pharmaceutical Company, Tabriz, Iran. Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Department of Basic Science, Maragheh University of Medical Sciences, Maragheh, Iran. Article History: Received: 9 June 2016 Revised: 1 February 2017 Accepted: 15 February 2017 ePublished: 13 April 2017
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