Novel therapeutic strategy targeting EpCAM-positive ovarian cancer stem cells

• Project/Area Number: 15K20151
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kumamoto University
• Principal Investigator: Motohara Takeshi 熊本大学, 大学院生命科学研究部(医), 講師 (10457591)
• Research Collaborator: Katabuchi Hidetaka
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 卵巣癌 / 癌幹細胞 / 抗癌剤治療抵抗性 / EpCAM / EpCAM陽性細胞

Outline of Final Research Achievements

Epithelial ovarian cancer is a highly lethal malignancy and overcoming chemoresistance is the major challenging in treating ovarian cancer patients. Even though ovarian cancer stem cells have not been completely elucidated, these cells are believed to play crucial roles in chemoresistance and relapse of ovarian cancer. Previous studies have supported the premise that EpCAM is one of the cell surface markers associated with cancer stem cells in many solid cancers, including ovarian cancer.
In this study, we demonstrated the functional role of EpCAM in the resistance to platinum-based chemotherapy. We also found that EpCAM-targeted therapies using adecatumumab showed a significant inhibition of ovarian cancer cell proliferation and tumor growth in in vitro assays and in vivo mouse models.
EpCAM expression may represent a promising therapeutic target to effectively extirpate the cancer stem cells as the root of ovarian cancer.

Academic Significance and Societal Importance of the Research Achievements

今回の研究では、卵巣癌におけるEpCAMの分子生物学的な役割として、特に抗癌剤治療抵抗性に密接に関わっていることを明らかにした。さらにわれわれは、EpCAM陽性の腫瘍細胞に対する新規分子標的薬が、EpCAM陽性の卵巣癌細胞に対する著明な抗腫瘍効果を有することを実験的に証明した。これらの結果は、EpCAMを標的とした有望な分子標的薬というツールを通じて、卵巣癌幹細胞を標的とした新たな治療戦略の開発に繋がっていくことが期待される。

Research Products

• [Journal Article] An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment. (2019)
  • Author(s): Motohara T, Masuda K, Morotti M, Zheng Y, El-Sahhar S, Chong KY, Wietek N, Alsaadi A, Karaminejadranjbar M, Hu Z, Artibani M, Gonzalez LS, Katabuchi H, Saya H, Ahmed AA.
  • Journal Title: Oncogene Volume: 38 Issue: 16 Pages: 2885-2898
  • DOI: 10.1038/s41388-018-0637-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Radical resection of an endometrioid carcinoma arising from endometriosis in the round ligament within the right canal of Nuck: a case report and literature review. (2018)
  • Author(s): Motooka Y, Motohara T, Honda R, Tashiro H, Mikami Y, Katabuchi H.
  • Journal Title: Gynecologic Oncology Reports Volume: 24 Pages: 61-64
  • DOI: 10.1016/j.gore.2018.01.010
  • Peer Reviewed
• [Journal Article] Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche. (2016)
  • Author(s): Miranda F, Motohara T (35人中33番目), et al.
  • Journal Title: Cancer Cell Volume: 30 Pages: 273-289
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rapid growing cystic ovarian metastasis from pancreatic cancer. (2016)
  • Author(s): Nomoto D, Hashimoto D, Motohara T, Chikamoto A, Nitta H, Beppu T, Katabuchi H
  • Journal Title: J Gastroenterol Hepatol Volume: 31 Issue: 4 Pages: 707-707
  • DOI: 10.1111/jgh.13164
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CD44 variant 6 is correlated with peritoneal dissemination and poor prognosis in patients with advanced epithelial ovarian cancer. (2015)
  • Author(s): Tjhay F, Motohara T, Tayama S, Narantuya D, Fujimoto K, Guo J, Sakaguchi I, Honda R, Tashiro H, Katabuchi H.
  • Journal Title: Cancer Sci Volume: 106 Issue: 10 Pages: 1421-1428
  • DOI: 10.1111/cas.12765
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Cancer stem cell marker EpCAM is involved in resistance to chemotherapy and poor prognosis in ovarian cancer patients (2018)
  • Author(s): Takeshi Motohara
  • Organizer: 29th Euro-Global Summit on Cancer Therapy & Radiation Oncology
• [Presentation] CD44 variant 6 is associated with peritoneal metastasis and poor prognosis in advanced ovarian cancer patients (2015)
  • Author(s): Takeshi Motohara, Shingo Tayama, Isao Sakaguchi, Hironori Tashiro, Hidetaka Katabuchi
  • Organizer: The 74th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Book] Emerging role of CD44 variant 6 in driving the metastatic journey of ovarian cancer stem cells. Cell Biology of the Ovary. (2018)
  • Author(s): Motohara T, Katabuchi H.
  • Total Pages: 166
  • Publisher: Springer
  • ISBN: 9789811079405