Analysis of ectopically expressed olfactly receptor in colon cancer stem cell

• Project/Area Number: 26860239
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: MORITA Rena 札幌医科大学, 医学部, 研究員 (00516916)
• 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 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 大腸がん幹細胞 / 嗅神経受容体 / OR7C1 / がん精巣抗原 / がん幹細胞 / 免疫療法 / 嗅神経レセプターファミリー / 伝達経路

Outline of Final Research Achievements

Colon cancer stem cells were isolated as side population (SP) cells. We identified Olfactory Receptor Family 7 Subfamily C Member 1 (OR7C1) is ectopically expressed in SP cells. Gene over expression analysis and gene knockdown analysis using siRNAs revealed that stem cell related genes including SOX2, OCT3/4 and LGR5 are located on the downstream of OR7C1. OR7C1 over expression activated PI3/AKT signal suggesting that OR7C1 uses PI3/AKT signal. Furthermore, OR7C1 is a novel cancer-testis antigen, and can be a target of cancer immunotherapy. These results indicate that OR7C1 has a role in the maintenance of colon cancer stem cells and can be a target of cancer immunotherapy.

Research Products

• [Journal Article] Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy (2016)
  • Author(s): Rena Morita, Yoshihiko Hirohashi, et al.
  • Journal Title: Clinical Cancer Research Volume: 1;22(13) Issue: 13 Pages: 3298-308
  • DOI: 10.1158/1078-0432.ccr-15-1709
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Establishment and analysis of cancer stem-like and non-cancer stem-like cells from the human colon cancer cell line SW480 (2016)
  • Author(s): Akari Takaya, Yoshihiko Hirohashi, et al.
  • Journal Title: PLOS One Volume: 14;11(7) Issue: 7 Pages: e0158903-e0158903
  • DOI: 10.1371/journal.pone.0158903
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Olfactory receptor family receptor, family 7, subfamily C, member 1 is a novel marker of colon cancer-initiating cells and is a potent target of immunotherapy (2016)
  • Author(s): Morita R, Hirohashi Y, Torigoe T, Inoda S, Takahashi A, Mariya T, Asanuma H, Tamura Y, Tsukahara T, Kanaseki T, Kubo T, Kutomi G, Mizuguchi T, Terui T, Ishitani K, Hashino S, Kondo T, Minagawa N, Takahashi N, Taketomi A, Todo S, Asaka M, Sato N.
  • Journal Title: Clin Cancer Res Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Prognostic impact of OR7C1, a new colon cancer stem cell marker, in primary human colorectal cancer (2015)
  • Author(s): Rena Morita
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30