Induction of mesenchymal to epithelial transition and suppression of cancer invasion by introduction of the reprogramming factors

• Project/Area Number: 25461698
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kochi University
• Principal Investigator: TAKAISHI MIKIRO 高知大学, 教育研究部医療学系臨床医学部門, 助教 (10303223)
• Co-Investigator(Kenkyū-buntansha): TERAISHI Mika 高知大学, 医学部付属病院, 特任助教 (40437736) ; MAKAJIMA Hideki 高知大学, 教育研究部医療学系臨床医学部門, 講師 (70314995) ; SANO Shigetoshi 高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: がん制御 / 間葉ー上皮移行 / 間葉－上皮移行 / 間葉-上皮移行

Outline of Final Research Achievements

Recent studies have indicated that mesenchymal to epithelial transition (MET) is observed during the generation of induced pluripotent stem cells by the reprogramming factors (RFs). In the present study, we investigated the effects of RFs on squamous cell carcinoma (SCC) cells. RFs-introduced cancer cells (RICs) demonstrated the enhanced epithelial characteristics in morphology with altered expression of molecular markers. The motility and invasive activities of RICs in vitro were significantly reduced. Furthermore, xenografts of RICs on immune deficient mice exhibited no lymph node metastasis, whereas metastasis was detected in parental SCC-inoculated mice. Thus, we concluded that RICs regained epithelial properties through MET and showed reduced cancer malignancy in vitro and in vivo. Therefore, the understanding of the MET process in cancer cells by introduction of RFs may lead to the designing of a novel anticancer strategy.

Research Products

• [Journal Article] Psoriatic inflammation facilitates the onset of arthritis in a mouse model. (2014)
  • Author(s): Yamamoto M, Nakajima K, Takaishi M, Kitaba S, Magata Y, Kataoka S, Sano S
  • Journal Title: J Invest Dermatol. Volume: 135 Issue: 2 Pages: 445-453
  • DOI: 10.1038/jid.2014.426
  • Peer Reviewed
• [Presentation] Attenuation of human SCC malignancy by introduction of reprogramming factors (2015)
  • Author(s): Mikiro Takaishi, Masahito Tarutani, Junji Takeda and Shigetoshi Sano
  • Organizer: 第29回表皮細胞研究会
  • Place of Presentation: 佐賀県、佐賀市、ホテルニューオータニ佐賀
  • Year and Date: 2015-11-14
• [Presentation] Attenuation of human SCC malignancy by introduction of reprogramming factors (2015)
  • Author(s): Mikiro Takaishi, Masahito Tarutani, Junji Takeda and Shigetoshi Sano
  • Organizer: The European Society for Dermatological Research
  • Place of Presentation: Postillion Convention Centre-WTC, Rotterdam, The Netherlands
  • Year and Date: 2015-09-09
  • Int'l Joint Research
• [Presentation] Epigenetic regulation of E-cadherin in the reprogramming gene-introduced cancer cells. (2014)
  • Author(s): Mikiro Takaishi, Masahito Tarutani, Junji Takeda and Shigetoshi Sano.
  • Organizer: The 39th Annual Meeting of the Japanese Society for Investigative Dermatology.
  • Place of Presentation: Hotel Hankyu Expopark, Suita, Osaka, Japan
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Introduction of the reprogramming factors into B16 murine melanoma cells attenuated in vivo metastasis through promoting mesencymal-epithelial transition (2013)
  • Author(s): Takaishi M, Tarutani M, Takeda J, Sano S
  • Organizer: International Investigative Dermatology
  • Place of Presentation: Edinburgh, Scotland, UK