Therapeutic targeting of tetraspanin8 in epithelial ovarian cancer invasion and metastasis

Oncogene
C S ParkS Lee

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 strateg...Continue Reading

References

Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S SzalaA J Linnenbach
Mar 8, 2000·Journal of Mammary Gland Biology and Neoplasia·J Albanell, J Baselga
Nov 3, 2001·Journal of Hepatology·K KanetakaS Hirohashi
Oct 11, 2003·Journal of Gastroenterology and Hepatology·Kengo KanetakaSetsuo Hirohashi
Apr 20, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sabine GesierichMargot Zöller
Jun 21, 2007·Molecular Cancer Research : MCR·Sebastian KuhnMargot Zöller
Nov 21, 2007·Molecular Cancer Therapeutics·Hung HuynhKhee Chee Soo
Jan 4, 2008·Histopathology·S J L PayneC A Wells
Mar 28, 2008·Clinical & Experimental Metastasis·Zhuan ZhouZhi-Hua Yang
Dec 17, 2008·Nature Reviews. Cancer·Margot Zöller
Mar 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Siân LennonBrian Leyland-Jones
Jan 27, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alberto Bardelli, Salvatore Siena
Jul 24, 2010·The American Journal of Pathology·Ernst Lengyel
Aug 20, 2011·Journal of the National Cancer Institute
Feb 15, 2012·Journal of Experimental & Clinical Cancer Research : CR·Ayako KimTakayuki Enomoto
Oct 3, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sukmook LeeJunho Chung
May 21, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Shijing YueMargot Zöller
Nov 20, 2013·Current Opinion in Obstetrics & Gynecology·Melissa C C Teo
Dec 21, 2013·Cancer Metastasis Reviews·Benoît ThibaultBettina Couderc
Feb 8, 2014·Nature Reviews. Cancer·Martin E Hemler
Oct 16, 2014·Drugs·Gillian M Keating

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Citations

Apr 4, 2017·Oncogenesis·G AgaësseI Masse
Mar 9, 2017·International Journal of Molecular Sciences·Mi Ra KimSukmook Lee
Feb 25, 2020·Cell Adhesion & Migration·Zehra Tavsan, Hülya Ayar Kayalı
Apr 21, 2017·Oncotarget·Aurelie Maisonial-BessetFrançoise Degoul
Dec 6, 2018·Nature Reviews. Clinical Oncology·Robin L AndersonUNKNOWN Cancer Research UK and Cancer Therapeutics CRC Australia Metastasis Working Group
Apr 29, 2019·Cancer Metastasis Reviews·Zhe Wang, Margot Zöller
Sep 8, 2017·Scientific Reports·Jihye JangSukmook Lee
Jun 28, 2018·Frontiers in Immunology·Felipe Vences-Catalán, Shoshana Levy
Jun 30, 2019·Nature Communications·Rongxuan ZhuHongxia Wang
Jan 27, 2019·Oncogene·Manale El KharbiliIngrid Masse
Dec 14, 2018·Journal of Experimental & Clinical Cancer Research : CR·Kun ZhaoMargot Zöller
Jan 11, 2020·Frontiers in Oncology·Wei MuMargot Zöller
Aug 30, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wenwu XiaoYuanpei Li
Jun 3, 2021·International Journal of Molecular Sciences·Kelly Pedrozo FerreiraKatia Candido Carvalho

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