Development of the therapy for cetuximab-resistant oral squamous cell carcinoma cells

• Project/Area Number: 26861579
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Keio University
• Principal Investigator: Yoshikawa Momoko 慶應義塾大学, 医学部(信濃町), 共同研究員 (50570967)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: CD44v / 口腔扁平上皮癌 / セツキシマブ / CD44ｖ / CD44

Outline of Final Research Achievements

Using cancer stem cell marker of CD44v positive oral squamous cell carcinoma cells, we prepared cetuximab-resistant oral squamous cell carcinoma cells. We analyzed changes in the characteristics of cancer stem cells associated with cetuximab resistance. In cetuximab-resistant cells, gene expression was similar to cells forming undifferentiated tumors with CD44v positivity as compared with the parent cells. Tumor tissues formed from cetuximab-resistant cells were undifferentiated tumors and were mostly CD44v positive cells. Consequently, it can be concluded that cetuximab-resistant cells display stronger characteristics of cancer stem cells than parent cells.

Research Products

• [Journal Article] Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines (2016)
  • Author(s): Ming Wang, Yutaka Miura, Kenji Tsuchihashi, Kazuki Miyano, Osamu Nagano, Momoko Yoshikawa, Ami Tanabe, Jun Makino, Yuki Mochida, Nobuhiro Nishiyama, Hideyuki Saya, Horacio Cabral, Kazunori Kataoka
  • Journal Title: Journal of Controlled Release Volume: 230 Pages: 26-33
  • DOI: 10.1016/j.jconrel.2016.03.038
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-) (2016)
  • Author(s): Tsuchihashi K, Okazaki S, Ohmura M, Ishikawa M, Sampetrean O, Onishi N, Wakimoto H, Yoshikawa M, Seishima R, Iwasaki Y, Morikawa T, Abe S, Takao A, Shimizu M, Masuko T, Nagane M, Furnari FB, Akiyama T, Suematsu M, Baba E, Akashi K, Saya H, Nagano O.
  • Journal Title: Cancer Research Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Ink4a/Arf-dependent Loss of Parietal Cells Induced by Oxidative Stress Promotes CD44-dependent Gastric Tumorigenesis. (2015)
  • Author(s): Seishima R, Wada T, Tsuchihashi K, Okazaki S, Yoshikawa M, Oshima H, Oshima M, Sato T, Hasegawa H, Kitagawa Y, Goldenring JR, Saya H, Nagano O.
  • Journal Title: Cancer Prevention Research Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] セツキシマブ耐性口腔扁平上皮癌細胞に対する治療の可能性 (2015)
  • Author(s): 吉川桃子、莇生田整治、森川暁、臼田慎、宮下英高、河奈裕正、中川種昭、佐谷秀行、永野修
  • Organizer: 第33回 日本口腔腫瘍学会 総会・学術大会
  • Place of Presentation: 奈良
  • Year and Date: 2015-01-30