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SV40 T/t-common polypeptide inhibits angiogenesis and growth of HER2-overexpressing human ovarian cancer

Cancer Gene Therapy volume 18, pages 859–870 (2011)Cite this article

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Abstract

Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed in human ovarian cancers and its overexpression is associated with increased angiogenesis, increased metastasis and reduced survival. Inhibition of HER2 in HER2-overexpressing cancers can lead to reduced angiogenesis and improved survival. Previously, we reported that SV40 T/t-common polypeptide has transcriptional repression activity and can inhibit HER2 expression. In this study, we investigated the effect of T/t-common on the angiogenesis-inducing activity of HER2-overexpressing human SK-OV-3 ovarian cancer cells. We found that compared to conditioned medium from control SK-OV-3 cancer cells, conditioned medium from T/t-common-expressing SK-OV-3 cells had a reduced ability to induce endothelial cell migration and tube formation in vitro and microvessel formation in vivo. These data indicate that T/t-common can inhibit the ability of SK-OV-3 cancer cells to induce angiogenesis. T/t-common was found to be able to downregulate the expression of several proangiogenic factors, including vascular endothelial growth factor-A, interleukin-8, basic fibroblast growth factor, matrix metalloproteinase-2 and urokinase-type plasminogen activator, and upregulate antiangiogenic factors, including thrombospondin-1 and tissue inhibitor of metalloproteinases-1 in SK-OV-3 cancer cells. Finally, we demonstrated that T/t-common could inhibit the angiogenesis and growth of HER2-overexpressing human ovarian tumor in NOD/SCID mice. Taken together, the data suggest that T/t-common had the potential to be developed as a new antiangiogenic agent specific for treating HER2-overexpressing ovarian cancers.

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Acknowledgements

We thank Jia-Ling Du for technical assistance and Dr Lih-Hwa Hwang for helpful discussion. This work was supported by grants NSC93-3112-B-002-014, NSC95-2320-B-002-093, NSC96-2320-B-002-035-MY3 and NSC96-2321-B-002-028-MY2 from National Science Council, Taiwan.

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  1. C-C Wen

    Present address: 2Current address: GeneTex, Hsinchu city, Taiwan.,

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  1. Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan

    S-P Hsueh, W-B Hsu, C-C Wen & W-B Wang

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Correspondence to W-B Wang.

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Hsueh, SP., Hsu, WB., Wen, CC. et al. SV40 T/t-common polypeptide inhibits angiogenesis and growth of HER2-overexpressing human ovarian cancer. Cancer Gene Ther 18, 859–870 (2011). https://doi.org/10.1038/cgt.2011.55

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