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Distinctive role of vasohibin-1A and its splicing variant vasohibin-1B in tumor angiogenesis

Cancer Gene Therapy volume 23, pages 133–141 (2016)Cite this article

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Abstract

Vasohibin-1 (VASH1) was isolated as a negative-feedback regulator of angiogenesis expressed in endothelial cells (ECs). There are two transcripts of VASH1, that is, the full-length VASH1A consisting of seven exons and the splicing variant VASH1B consisting of four exons. Here, we compared the effects of VASH1A and VASH1B on tumor angiogenesis. When ECs were transfected with VASH1A or VASH1B cDNAs, VASH1B transfectants, but not VASH1A ones, induced autophagic cell death of ECs. With sonoporation, the VASH1A or VASH1B gene were transfected specifically in ECs of tumor vessels in mice. Both VASH1A and VASH1B decreased tumor vessel density and inhibited tumor growth. VASH1A normalized the remaining tumor vessels, increased their rate of perfusion, decreased tumor hypoxia and enhanced the efficacy of anticancer chemotherapy, whereas VASH1B pruned tumor vessels without causing normalization, increased tumor hypoxia and tumor necrosis and did not enhance the efficacy of anticancer chemotherapy. The alternate transfection of mice with the VASH1A and VASH1B gene showed the highest effects on antitumor activity and normalization of tumor vessels. Our present findings on VASH1A and VASH1B should provide an innovative approach that would improve the efficacy of antiangiogenic cancer therapy by balancing vascular normalization and pruning.

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Acknowledgements

This work was supported by a research program of the Project for Development of Innovative Research on Cancer Therapy (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan (to YS); and a grant-in-aid (24800003) from Japan Society for Research Activity Start-up (to SH).

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Authors and Affiliations

  1. Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

    S Horie, Y Suzuki, M Kobayashi & Y Sato

  2. Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Tokyo, Japan

    T Kadonosono & S Kondoh

  3. Department of Biomedical Engineering, Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan

    T Kodama

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  1. S Horie
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  2. Y Suzuki
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  3. M Kobayashi
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  6. T Kodama
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  7. Y Sato
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Correspondence to Y Sato.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website

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Horie, S., Suzuki, Y., Kobayashi, M. et al. Distinctive role of vasohibin-1A and its splicing variant vasohibin-1B in tumor angiogenesis. Cancer Gene Ther 23, 133–141 (2016). https://doi.org/10.1038/cgt.2016.13

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