Immunological aspects of cancer stem cell and spermatogenesis

• Project/Area Number: 15H04722
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Sapporo Medical University
• Principal Investigator: HIROHASHI Yoshihiko 札幌医科大学, 医学部, 准教授 (30516901)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: がん幹細胞 / 免疫療法 / 班精巣抗原 / がん精巣抗原 / 細胞障害性Ｔ細胞 / OR7C1 / BORIS / CTL

Outline of Final Research Achievements

In this research project, we isolated highly tumorigenic cancer stem cells from human colon cancer, cervical cancer and lung cancer cells. We examined the expression profiles of cancer stem cells by cDNA microarry, and we found that numbers of testis-related genes are expressed in cancer stem cells. Those are OR7C1, BORIS SMCP and DNAJB8. Importantly, gene specific knockdown using siRNAs revealed that testis-related genes have important role in the maintenance of cancer stem cells. And we also identified testis-related gene products can be targeted by immunotherapy. These results indicate that immunotherapy targeting testis-related gene products is a promising approach to target cancer stem cells.

Research Products

• [Journal Article] Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1 (2018)
  • Author(s): Kusumoto Hiroki、Hirohashi Yoshihiko、Nishizawa Satoshi、Yamashita Masamichi、Yasuda Kazuyo、Murai Aiko、Takaya Akari、Mori Takashi、Kubo Terufumi、Nakatsugawa Munehide、Kanaseki Takayuki、Tsukahara Tomohide、Kondo Toru、Sato Noriyuki、Hara Isao、Torigoe Toshihiko
  • Journal Title: Cancer Science Volume: 109 Issue: 3 Pages: 741-750
  • DOI: 10.1111/cas.13501
  • Peer Reviewed / Open Access
• [Journal Article] ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway. (2017)
  • Author(s): Ogawa T, Hirohashi Y, Murai A, Nishidate T, Okita K, Wang L, Ikehara Y, Satoyoshi T, Usui A, Kubo T, Nakastugawa M, Kanaseki T, Tsukahara T, Kutomi G, Furuhata T, Hirata K, Sato N, Mizuguchi T, Takemasa I, Torigoe T.
  • Journal Title: Oncotarget Volume: 8 Issue: 68 Pages: 112550-112564
  • DOI: 10.18632/oncotarget.22545
  • Peer Reviewed / Open Access
• [Journal Article] Identification of antigenic peptides from novel renal cancer stem-like cell antigen, DNAJB8 (2017)
  • Author(s): Nishizawa S, Hirohashi Y, Kusumoto H, Wakamiya T, Iguchi T, Yamashita S, Iba A, Kikkawa K, Kohjimoto Y, Torigoe T, Hara I
  • Journal Title: Biochem Biophys Res Commun Volume: 494 Issue: 3-4 Pages: 693-699
  • DOI: 10.1016/j.bbrc.2017.10.146
  • Peer Reviewed
• [Journal Article] Comprehensive single-cell transcriptome analysis reveals heterogeneity in endometrioid adenocarcinoma tissues. (2017)
  • Author(s): Hashimoto S, Tabuchi Y, Yurino H, Hirohashi Y, Deshimaru S, Asano T, Mariya T, Oshima K, Takamura Y, Ukita Y, Ametani A, Kondo N, Monma N, Takeda T, Misu S, Okayama T, Ikeo K, Saito T, Kaneko S, Suzuki Y, Hattori M, Matsushima K, et al.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 14225-14225
  • DOI: 10.1038/s41598-017-14676-3
  • Peer Reviewed / Open Access
• [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 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] Plasticity of lung cancer stem-like cells is regulated by the transcription factor HOXA5 that is induced by oxidative stress (2016)
  • Author(s): Hiroshi Saijo, Yoshihiko Hirohashi, et al.
  • Journal Title: Oncotarget Volume: 2;7(31) Issue: 31 Pages: 50043-50056
  • DOI: 10.18632/oncotarget.10571
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation. (2016)
  • Author(s): Yasuda K, Hirohashi Y, Kuroda T, Takaya A, Kubo T, Kanaseki T, Tsukahara T, Hasegawa T, Saito T, Sato N, Torigoe T.
  • Journal Title: Biochem Biophys Res Commun Volume: 472 Issue: 4 Pages: 643-647
  • DOI: 10.1016/j.bbrc.2016.03.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer. (2016)
  • Author(s): Mariya T, Hirohashi Y, Torigoe T, Tabuchi Y, Asano T, Saijo H, Kuroda T, Yasuda K, Mizuuchi M, Saito T, Sato N
  • Journal Title: Oncotarget Volume: in press Issue: 18 Pages: 1-17
  • DOI: 10.18632/oncotarget.8645
  • 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
• [Journal Article] 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. (2016)
  • Author(s): Asano T, Hirohashi Y, Torigoe T, Mariya T, Horibe R, Kuroda T, Tabuchi Y, Saijo H, Yasuda K, Mizuuchi M, Takahashi A, Asanuma H, Hasegawa T, Saito T, Sato N.
  • Journal Title: Oncotarget Volume: 7 Issue: 10 Pages: 11223-11237
  • DOI: 10.18632/oncotarget.7165
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immune responses to human cancer stem-like cells/cancer-initiating cells. (2016)
  • Author(s): Hirohashi Y, Torigoe T, Tsukahara T, Kanaseki T, Kochin V, Sato N
  • Journal Title: Cancer Sci Volume: 107 Issue: 1 Pages: 12-17
  • DOI: 10.1111/cas.12830
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] がん幹細胞に注目したがん免疫療法 (2017)
  • Author(s): 廣橋良彦、塚原智英、金関貴幸、中津川宗秀、久保輝文、鳥越俊彦
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Immunoreaction to cancer stem cells (2017)
  • Author(s): 廣橋良彦
  • Organizer: 第63回日本病理学会秋期特別総会
• [Presentation] 癌精巣抗原BORISは婦人科癌幹細胞性に関与し、免疫療法のターゲットになりうる (2017)
  • Author(s): 廣橋良彦、浅野拓也、鳥越俊彦
  • Organizer: 第56回日本臨床細胞学会秋期大会
• [Presentation] がん精巣抗原は、がん幹細胞標的免疫療法の有力な候補になる (2016)
  • Author(s): 廣橋 良彦
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（仙台市）
• [Presentation] がん幹細胞標的免疫療法の開発 (2016)
  • Author(s): 廣橋 良彦
  • Organizer: 第14回日本臨床腫瘍学会学術集会
  • Place of Presentation: 神戸国際展示場・神戸国際会議場（神戸市）
  • Invited
• [Presentation] 癌精巣抗原BORISの肺癌幹細胞様細胞における発現とBORIS抗原を標的とした免疫療法の検討 (2016)
  • Author(s): 堀部 亮多、廣橋 良彦
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪国際交流センター（大阪市）
• [Presentation] がん幹細胞を標的とした免疫療法 (2015)
  • Author(s): 廣橋良彦
  • Organizer: 第５回北海道探索病理学研究シンポジウム
  • Place of Presentation: ニューオータニイン札幌（札幌市）
  • Year and Date: 2015-10-24
  • Invited
• [Presentation] Establishment of cancer stem cell-targeting immunotherapy (2015)
  • Author(s): 廣橋良彦
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: ロイトン札幌（札幌市）
  • Year and Date: 2015-07-16
  • Invited
• [Presentation] 免疫療法でがんは治せるのか？ ~次世代のがん免疫療法~ (2015)
  • Author(s): 廣橋良彦
  • Organizer: 日本耳鼻咽喉科学会第９８回和歌山地方部会総会
  • Place of Presentation: 和歌山県民文化会館（和歌山市）
  • Year and Date: 2015-07-05
  • Invited