Inhibition of ascites tumor growth in vivo by sTie-2 is potentiated by a combinatorial therapy with sFLT-1

D'Souza, Saritha Sandra and Gururaj, Anupama E. and Raj, Harsha M. and Rössler, Jochen and Salimath, Bharathi P. (2010) Inhibition of ascites tumor growth in vivo by sTie-2 is potentiated by a combinatorial therapy with sFLT-1. The Journal of Gene Medicine, 12 (12). pp. 968-980. ISSN 1521-2254

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Official URL: http://doi.org/10.1002/jgm.1520

Abstract

Abstract Background Inhibition of tumor angiogenesis is a promising approach for cancer therapy and the Tie-2/angiopoietin pathway appears to play an important role. In the present study, we have developed strategies to explore the therapeutic potential of blocking the Tie-2/angiopoietin pathway by sTie-2. Methods Ehrlich ascites tumor (EAT) cells were stably transfected to overexpress a truncated form of sTie-2. Transfectants were characterized for their in vitro growth behavior and transplanted into nude mice. Furthermore, recombinant sTie-2 produced by the baculovirus expression system was used to sequester angiopoietins in the murine ascites carcinoma model. The effect of sTie-2 treatment alone or in combination with sFLT-1 on the weight of the animal, ascites cell number and volume was studied. Results EAT cells stably transfected with a truncated form of sTie-2 showed no change in cell proliferation in vitro and colony forming in soft agar compared to control cells. However, sTie-2 transfected EAT cells transplanted into nude mice reduced tumor burden and demonstrated a reduction in ascites formation and peritoneal angiogenesis. Recombinant sTie-2 showed angiogenic activity in the tube formation and wound healing assay in vitro. sTie-2 treatment alone or in combination with sFLT-1 in an ascites tumor mouse model resulted in reduced peritoneal angiogenesis, with a concomitant decrease in tumor cell number, volume of ascites and the number of invasive tumor cells, as assayed by CD31 staining. Conclusions The findings of the present study demonstrate an important role for the Tie-2/angiopoietin pathway in the formation of tumor vasculature and suggest that sTie-2 might yield useful anticancer therapy. Copyright © 2010 John Wiley & Sons, Ltd.

Item Type: Article
Uncontrolled Keywords: angiopoietins, recombinant sTie-2, sFLT-1, angiogenesis, ascites
Subjects: B Life Science > Biotechnology
Divisions: Department of > Biotechnology
Depositing User: lpa manjunath user
Date Deposited: 29 Jul 2019 10:08
Last Modified: 29 Jul 2019 10:08
URI: http://eprints.uni-mysore.ac.in/id/eprint/6187

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