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T11TS impedes glioma angiogenesis by inhibiting VEGF signaling and pro-survival PI3K/Akt/eNOS pathway with concomitant upregulation of PTEN in brain endothelial cells

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Abstract

The crucial role of angiogenesis in malignant glioma progression makes it a potential target of therapeutic intervention in glioma. Previous studies from our lab showed that sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) has potent anti-neoplastic and immune stimulatory effects in rodent glioma model. In the present study we investigated the anti-angiogenic potential of T11TS and deciphered the underlying molecular mechanism of its anti-angiogenic action in malignant glioma. Vascular endothelial growth factor (VEGF) signaling is crucial for initiating tumor angiogenic responses. The present preclinical study was designed to evaluate the effect of T11TS therapy on VEGF and VEGFR-2 expression in glioma associated brain endothelial cells and to determine the effects of in vivo T11TS administration on expression of PTEN and downstream pro-survival PI3K/Akt/eNOS pathway proteins in glioma associated brain endothelial cells. T11TS therapy in rodent glioma model significantly downregulated expression of VEGF along with its receptor VEGFR-2 and inhibited the expression of pro-survival PI3K/Akt/eNOS proteins in glioma associated brain endothelial cells. Furthermore, T11TS therapy in glioma induced rats significantly upregulated brain endothelial cell PTEN expression, inhibited eNOS phosphorylation and production of nitric oxide in glioma associated brain endothelial cells. Taken together our findings suggest that T11TS can be introduced as an effective angiogenesis inhibitor in human glioma as T11TS targets multiple levels of angiogenic signaling cascade impeding glioma neovascularisation.

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Acknowledgments

The study was supported by funding from the Department of Science and Technology (DST) Govt. of India. The authors wish to thank Dr. Pijush Kanti Das, Chief Scientist and Head of Infectious Disease and Immunology Division at the CSIR-Indian Institute of Chemical Biology for providing immunofluorescence imaging facilities and some monoclonal antibodies. The authors also wish to thank Ms. Shreyasi Palit, senior research fellow at CSIR-IICB for technical help.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Immunology Research Laboratory, Department of Laboratory Medicine, School of Tropical Medicine, 108 C. R. Avenue, Kolkata, 700073, India

    Debanjan Bhattacharya, Manoj Kumar Singh, Suhnrita Chaudhuri, Sagar Acharya & Swapna Chaudhuri

  2. Department of Biochemistry and Medical Biotechnology, School of Tropical Medicine, 108 C. R. Avenue, Kolkata, 700073, India

    Anjan Kumar Basu

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  1. Debanjan Bhattacharya
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Correspondence to Swapna Chaudhuri.

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Bhattacharya, D., Singh, M.K., Chaudhuri, S. et al. T11TS impedes glioma angiogenesis by inhibiting VEGF signaling and pro-survival PI3K/Akt/eNOS pathway with concomitant upregulation of PTEN in brain endothelial cells. J Neurooncol 113, 13–25 (2013). https://doi.org/10.1007/s11060-013-1095-5

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