PMID- 26849232 OWN - NLM STAT- MEDLINE DCOM- 20171206 LR - 20210325 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 10 DP - 2016 Mar 8 TI - Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is involved in cervical cancer stemness and can be a target of immunotherapy. PG - 11223-37 LID - 10.18632/oncotarget.7165 [doi] AB - Cervical cancer is a major cause of cancer death in females worldwide. Cervical cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are resistant to conventional radiotherapy and chemotherapy, and CSCs/CICs are thought to be responsible for recurrence. Eradication of CSCs/CICs is thus essential to cure cervical cancer. In this study, we isolated cervical CSCs/CICs by sphere culture, and we identified a cancer testis (CT) antigen, CTCFL/BORIS, that is expressed in cervical CSCs/CICs. BORIS has 23 mRNA isoform variants classified by 6 subfamilies (sfs), and they encode 17 different BORIS peptides. BORIS sf1 and sf4 are expressed in both CSCs/CICs and non-CSCs/CICs, whereas BORIS sf6 is expressed only in CSCs/CICs. Overexpression of BORIS sf6 in cervical cancer cells increased sphere formation and tumor-initiating ability compared with those in control cells, whereas overexpression of BORIS sf1 and BORIS sf4 resulted in only slight increases. Thus, BORIS sf6 is a cervical CSC/CIC-specific subfamily and has a role in the maintenance of cervical CSCs/CICs. BORIS sf6 contains a specific c-terminal domain (C34), and we identified a human leukocyte antigen (HLA)-A2-restricted antigenic peptide, BORIS C34_24(9) encoded by BORIS sf6. A BORIS C34_24(9)-specific cytotoxic T cell (CTL) clone showed cytotoxicity for BORIS sf6-overexpressing cervical cancer cells. Furthermore, the CTL clone significantly suppressed sphere formation of CaSki cells. Taken together, the results indicate that the CT antigen BORIS sf6 is specifically expressed in cervical CSCs/CICs, that BORIS sf6 has a role in the maintenance of CSCs/CICs, and that BORIS C34_24(9) peptide is a promising candidate for cervical CSC/CIC-targeting immunotherapy. FAU - Asano, Takuya AU - Asano T AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Obsterics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Hirohashi, Yoshihiko AU - Hirohashi Y AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Torigoe, Toshihiko AU - Torigoe T AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Mariya, Tasuku AU - Mariya T AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Obsterics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Horibe, Ryota AU - Horibe R AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Kuroda, Takafumi AU - Kuroda T AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Obsterics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Tabuchi, Yuta AU - Tabuchi Y AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Obsterics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Saijo, Hiroshi AU - Saijo H AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Yasuda, Kazuyo AU - Yasuda K AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Mizuuchi, Masahito AU - Mizuuchi M AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Obsterics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Takahashi, Akari AU - Takahashi A AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Asanuma, Hiroko AU - Asanuma H AD - Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Hasegawa, Tadashi AU - Hasegawa T AD - Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Saito, Tsuyoshi AU - Saito T AD - Obsterics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Sato, Noriyuki AU - Sato N AD - Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (CTCFL protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (Protein Isoforms) SB - IM MH - Adult MH - Aged MH - Animals MH - Carcinoma, Squamous Cell/metabolism/*pathology MH - DNA-Binding Proteins/*immunology/*metabolism MH - Female MH - Heterografts MH - Humans MH - Mice, Inbred BALB C MH - Mice, Nude MH - Middle Aged MH - Neoplastic Stem Cells/immunology/metabolism/pathology MH - Protein Isoforms MH - Uterine Cervical Neoplasms/metabolism/*pathology PMC - PMC4905468 OTO - NOTNLM OT - BORIS OT - CTL OT - cancer stem cells OT - cervical cancer OT - peptide vaccine COIS- CONFLICTS OF INTEREST The authors have no financial conflicts of interest. EDAT- 2016/02/06 06:00 MHDA- 2017/12/07 06:00 PMCR- 2016/03/08 CRDT- 2016/02/06 06:00 PHST- 2015/08/24 00:00 [received] PHST- 2016/01/19 00:00 [accepted] PHST- 2016/02/06 06:00 [entrez] PHST- 2016/02/06 06:00 [pubmed] PHST- 2017/12/07 06:00 [medline] PHST- 2016/03/08 00:00 [pmc-release] AID - 7165 [pii] AID - 10.18632/oncotarget.7165 [doi] PST - ppublish SO - Oncotarget. 2016 Mar 8;7(10):11223-37. doi: 10.18632/oncotarget.7165.