Rena Morita 1 , Yoshihiko Hirohashi 2 , Toshihiko Torigoe 2 , Satoko Ito-Inoda 1 , Akari Takahashi 1 , Tasuku Mariya 1 , Hiroko Asanuma 1 , Yasuaki Tamura 1 , Tomohide Tsukahara 1 , Takayuki Kanaseki 1 , Terufumi Kubo 1 , Goro Kutomi 3 , Toru Mizuguchi 3 , Takeshi Terui 4 , Kunihiko Ishitani 4 , Satoshi Hashino 5 , Toru Kondo 6 , Nozomi Minagawa 7 , Norihiko Takahashi 7 , Akinobu Taketomi 7 , Satoru Todo 7 , Masahiro Asaka 5 , Noriyuki Sato 1 Show Affiliations »
Abstract
PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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. ©2016 American Association for Cancer Research.
PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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. ©2016 American Association for Cancer Research.
Entities: Chemical
Disease
Gene
Species
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Year: 2016
PMID： 26861454 DOI： 10.1158/1078-0432.CCR-15-1709
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531