title: Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy.
abstract: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy.
  
  
  
  Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model.
  
  
  
  OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1-negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide-specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model.
  
  
  
  OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. ©2016 AACR.
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Rena
authors: R
authors: Morita
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan. hirohash@sapmed.ac.jp torigoe@sapmed.ac.jp.
authors: Yoshihiko
authors: Y
authors: Hirohashi
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan. hirohash@sapmed.ac.jp torigoe@sapmed.ac.jp.
authors: Toshihiko
authors: T
authors: Torigoe
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Satoko
authors: S
authors: Ito-Inoda
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Akari
authors: A
authors: Takahashi
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Tasuku
authors: T
authors: Mariya
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Hiroko
authors: H
authors: Asanuma
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Yasuaki
authors: Y
authors: Tamura
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Tomohide
authors: T
authors: Tsukahara
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Takayuki
authors: T
authors: Kanaseki
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Terufumi
authors: T
authors: Kubo
authors: Department of Surgery, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Goro
authors: G
authors: Kutomi
authors: Department of Surgery, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Toru
authors: T
authors: Mizuguchi
authors: Higashi-Sapporo Hospital, Shiroishi-ku, Sapporo, Japan.
authors: Takeshi
authors: T
authors: Terui
authors: Higashi-Sapporo Hospital, Shiroishi-ku, Sapporo, Japan.
authors: Kunihiko
authors: K
authors: Ishitani
authors: Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Kita-Ku, Sapporo, Japan.
authors: Satoshi
authors: S
authors: Hashino
authors: Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Kita-Ku, Sapporo, Japan.
authors: Toru
authors: T
authors: Kondo
authors: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita-Ku, Sapporo, Japan.
authors: Nozomi
authors: N
authors: Minagawa
authors: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita-Ku, Sapporo, Japan.
authors: Norihiko
authors: N
authors: Takahashi
authors: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita-Ku, Sapporo, Japan.
authors: Akinobu
authors: A
authors: Taketomi
authors: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita-Ku, Sapporo, Japan.
authors: Satoru
authors: S
authors: Todo
authors: Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Kita-Ku, Sapporo, Japan.
authors: Masahiro
authors: M
authors: Asaka
authors: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-Ku, Sapporo, Japan.
authors: Noriyuki
authors: N
authors: Sato
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019073:HT29 Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000276:immunology*; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018035:Receptors, Odorant / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018874:Spheroids, Cellular; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D018035:Receptors, Odorant