Abstract
Maspin, a non-inhibitory member of serine protease family, acts as an effective tumor suppressor by inhibiting cell inhesion and mobility. We found that exogenous wild-type rMaspin had a low effect on tumor growth in vivo. However, when the peptide Arg-Gly-Asp-hexahistidine (RGD-6His) was introduced into rMaspin, the modified rMaspin showed significant inhibitory activity in angiogenic assays and tumor-bearing animal models. Overall, our data suggested that both the RGD and hexahistidine fragments contributed to improve the fusion protein activity and polyhistidine peptide could be considered as flexible linker to separate RGD and Maspin moieties to avoid function interference. Besides, it is an efficient tag to achieve purified recombinant proteins. Furthermore, rMaspin fusing with RGD and hexahistidine could be a viable anticancer candidate.
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Acknowledgments
This work was partly supported by grants from The Natural Science Fundation of Jiangsu Province (BK20130395, BK2012232), The National Natural Science Fundation of China (81402189, 81202467, 81202879), Jiangsu Overseas Research & Training Program for University Prominent Young & Middle-aged Teachers and Presidents and the Priority Academic Program Development of Jiangsu Higher Education Institutions. Dr. Yin is especially grateful to Dr. Margaret Worrall (University College Dublin, Ireland) for providing plasmids containing human Maspin.
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Yin, R., Guo, L., Zhang, J. et al. RGD and polyhistidine tumor homing peptides potentiates the action of human Maspin as an antineoplastic candidate. Appl Microbiol Biotechnol 100, 6209–6218 (2016). https://doi.org/10.1007/s00253-016-7345-7
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DOI: https://doi.org/10.1007/s00253-016-7345-7