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Therapeutic targeting of tetraspanin8 in epithelial ovarian cancer invasion and metastasis

Oncogene volume 35, pages 4540–4548 (2016)Cite this article

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Abstract

Epithelial ovarian cancer (EOC) invasion and metastasis are complex phenomena that result from the coordinated action of many metastatic regulators and must be overcome to improve clinical outcomes for patients with these cancers. The identification of novel therapeutic targets is critical because of the limited success of current treatment regimens, particularly in advanced-stage ovarian cancers. In this study, we found that tetraspanin 8 (TSPAN8) is overexpressed in about 52% (14/27) of EOC tissues and correlates with poor survival. Using small interfering RNA-mediated TSPAN8 knockdown and a competition assay with purified TSPAN8 large extracellular loop (TSPAN8–LEL) protein, we identified TSPAN8–LEL as a key regulator of EOC cell invasion. Furthermore, monotherapy with TSPAN8-blocking antibody we developed shows that antibody-based modulation of TSPAN8–LEL can significantly reduce the incidence of EOC metastasis without severe toxicity in vivo. Finally, we demonstrated that the TSPAN8-blocking antibody promotes the internalization and concomitant downregulation of cell surface TSPAN8. Collectively, our data suggest TSPAN8 as a potential novel therapeutic target in EOCs and antibody targeting of TSPAN8 as an effective strategy for inhibiting invasion and metastasis of TSPAN8-expressing EOCs.

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Acknowledgements

This work was supported by a research grant (10TS03) from the Scripps Korea Antibody Institute.

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Author notes

  1. C S Park

    Present address: 5Current address: Eco & Bio Convergence Team, Korea Institute of Ceramic Engineering and Technology, 101 Soho-ro, Jinju-si, Gyeongsangnam-do 661-031, Korea.,

  2. C S Park and T-K Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute,, Chuncheon-si, Korea

    C S Park, T-K Kim, M H Jeoung, W R Lee, N K Go & S Lee

  2. New Experimental Therapeutics Branch, Research Institute, National Cancer Center, Goyang-si, Korea

    H G Kim & K Heo

  3. Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang-si, Korea

    Y-J Kim

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  1. C S Park
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Correspondence to K Heo or S Lee.

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Park, C., Kim, TK., Kim, H. et al. Therapeutic targeting of tetraspanin8 in epithelial ovarian cancer invasion and metastasis. Oncogene 35, 4540–4548 (2016). https://doi.org/10.1038/onc.2015.520

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