Comprehensive understanding of interstitial signals between cancer and interstitium

• Project/Area Number: 16H02481
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical genome science
• Research Institution: The University of Tokyo (2018-2020); Tokyo Medical and Dental University (2016-2017)
• Principal Investigator: Ishikawa Shumpei 東京大学, 大学院医学系研究科(医学部), 教授 (50418638)
• Project Period (FY): 2016-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000); Fiscal Year 2020: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2019: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2018: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2017: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2016: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: ゲノム創薬

Outline of Final Research Achievements

Cancer cells receive signals from surrounding stromal cells in vivo, and conversely, the cancer cells themselves induce stromal cells suitable for survival. In this study, based on the mouse / human-derived sequence separation method developed by the applicant so far, the global view and diversity of cancer-stromal interactions in Xenograft of various cancer types, including PDX, was analyzed at the genomic level. We also developed interactome analysis methods among different cell types from the single cell transcriptome data, and analyzed cancer tissues homeostatic microenvironment. As a result, we were able to find and experimentally verify new important molecules responsible for cancer-stromal interactions in several cancer types.

Academic Significance and Societal Importance of the Research Achievements

がん細胞はそれ単独での生存は難しく、生体内では常に周囲の間質細胞からの支持シグナルを受け、また逆にがん細胞自身がシグナルを出して生存に適した間質細胞を誘導しています。本研究ではそのようながん細胞と間質細胞との相互作用の全体像を、由来細胞種別に遺伝子発現解析を行う技術を用いて解析し、がん細胞と間質細胞とを含むがん組織の恒常性のメカニズムを明らかにするとともに、治療標的となる重要な相互作用分子を解明しました。

Research Products

• [Int'l Joint Research] National Taiwan Univ. of Sci. & Tech.(台湾)
• [Journal Article] High levels of human epididymis protein 4 mRNA and protein expression are associated with chemoresistance and a poor prognosis in pancreatic cancer (2020)
  • Author(s): Ohkuma Ryotaro、Yoshimura Kiyoshi、他
  • Journal Title: International Journal of Oncology Volume: 58 Issue: 1 Pages: 57-69
  • DOI: 10.3892/ijo.2020.5147
  • Peer Reviewed / Open Access
• [Journal Article] Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases (2020)
  • Author(s): Atsumi Shinichiro、Katoh Hiroto、Komura Daisuke、Hashimoto Itaru、Furuya Genta、Koda Hirotomo、Konishi Hiroki、Suzuki Ryohei、Yamamoto Asami、Yuba Satsuki、Abe Hiroyuki、Rino Yasushi、Oshima Takashi、Ushiku Tetsuo、Fukayama Masashi、Seto Yasuyuki、Ishikawa Shumpei
  • Journal Title: Communications Biology Volume: 3 Issue: 1 Pages: 588-588
  • DOI: 10.1038/s42003-020-01305-5
  • Peer Reviewed / Open Access
• [Journal Article] High expression levels of polymeric immunoglobulin receptor are correlated with chemoresistance and poor prognosis in pancreatic cancer (2020)
  • Author(s): Ohkuma Ryotaro、Yoshimura Kiyoshi、他
  • Journal Title: Oncology Reports Volume: 44 Issue: 1 Pages: 252-262
  • DOI: 10.3892/or.2020.7610
  • Peer Reviewed / Open Access
• [Journal Article] The first case of gastric carcinoma with NTRK rearrangement: identification of a novel ATP1B-NTRK1 fusion. (2020)
  • Author(s): Shinozaki-Ushiku A, Ishikawa S, Komura D, Seto Y, Aburatani H, Ushiku T.
  • Journal Title: Gastric Cancer. Volume: 23 Issue: 5 Pages: 944-947
  • DOI: 10.1007/s10120-020-01061-9
  • Peer Reviewed
• [Journal Article] Defined lifestyle and germline factors predispose Asian populations to gastric cancer (2020)
  • Author(s): Suzuki A, Katoh H, Komura D, Kakiuchi M, Tagashira A, Yamamoto S, Tatsuno K, Ueda H, Nagae G, Fukuda S, Umeda T, Totoki Y, Abe H, Ushiku T, Matsuura T, Sakai E, Ohshima T, Nomura S, Seto Y, Shibata T, Rino Y, Nakajima A, Fukayama M, Ishikawa S, Aburatani H.
  • Journal Title: Science Advances Volume: 6 Issue: 19 Pages: 9778-9778
  • DOI: 10.1126/sciadv.aav9778
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel targets identified by integrated cancer-stromal interactome analysis of pancreatic adenocarcinoma. (2020)
  • Author(s): Hiroshima Y, Kasajima R, Kimura Y, Komura D, Ishikawa S, Ichikawa Y, Bouvet M, Yamamoto N, Oshima T, Morinaga S, Singh SR, Hoffman RM, Endo I, Miyagi Y.
  • Journal Title: Cancer Lett. Volume: 469 Pages: 217-227
  • DOI: 10.1016/j.canlet.2019.10.031
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] In vivo effects of mutant RHOA on tumor formation in an orthotopic inoculation model. (2019)
  • Author(s): Nishizawa T, Nakano K, Fujii E, Komura D, Kuroiwa Y, Ishimaru C, Monnai M, Aburatani H, Ishikawa S, Suzuki M.
  • Journal Title: Oncol Rep. Volume: 42 Pages: 1745-1754
  • DOI: 10.3892/or.2019.7300
  • Peer Reviewed / Open Access
• [Journal Article] Difference in morphology and interactome profiles between orthotopic and subcutaneous gastric cancer xenograft models (2018)
  • Author(s): Nakano, Kiyotaka, Takashi Nishizawa, Daisuke Komura, Etsuko Fujii, Makoto Monnai, Atsuhiko Kato, Shin-Ichi Funahashi, Shumpei Ishikawa, and Masami Suzuki
  • Journal Title: Journal of Toxicologic Pathology Volume: 31 Issue: 4 Pages: 293-300
  • DOI: 10.1293/tox.2018-0020
  • NAID: 130007497156
  • ISSN: 0914-9198, 1881-915X
  • Peer Reviewed / Open Access
• [Journal Article] Machine learning methods for histopathological image analysis (2018)
  • Author(s): Komura D, Ishikawa S
  • Journal Title: Computational and Structural Biotechnology Journal Volume: 16 Pages: 34-42
  • DOI: 10.1016/j.csbj.2018.01.001
  • Peer Reviewed / Open Access
• [Journal Article] Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor (2017)
  • Author(s): Y. Shikata Y, T. Yoshimaru, M. Komatsu, H. Katoh, R. Sato, S. Kanagaki, Y. Okazaki, S. Toyokuni, E. Tashiro, S. Ishikawa, T. Katagiri, M. Imoto,
  • Journal Title: Cancer Science Volume: 108 Issue: 4 Pages: 785-794
  • DOI: 10.1111/cas.13175
  • NAID: 120006535004
  • Peer Reviewed / Open Access
• [Journal Article] A Benchmark for Comparing Precision Medicine Methods in Thyroid Cancer Diagnosis using Tissue Microarrays. (2017)
  • Author(s): Ching-Wei Wang, Yu-Ching Lee, Evelyne Calista, Fan Zhou, Hongtu Zhu, Ryohei Suzuki, Daisuke Komura, Shumpei Ishikawa, Shih-Ping Cheng
  • Journal Title: Bioinformatics Volume: 34 Issue: 10 Pages: 1767-1773
  • DOI: 10.1093/bioinformatics/btx838
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genomic pathobiology of gastric carcinoma. (2017)
  • Author(s): Katoh H, Ishikawa S.
  • Journal Title: Pathol Int. Volume: 67 Issue: 2 Pages: 63-63
  • DOI: 10.1111/pin.12493
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CASTIN: a system for comprehensive analysis of cancer-stromal interactome. (2016)
  • Author(s): Komura D, Isagawa T, Kishi K, Suzuki R, Sato R, Tanaka M, Katoh H, Yamamoto S, Tatsuno K, Fukayama M, Aburatani H, Ishikawa S
  • Journal Title: BMC Genomics Volume: 17 Issue: 1 Pages: 899-899
  • DOI: 10.1186/s12864-016-3207-z
  • Peer Reviewed / Open Access
• [Journal Article] Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma. (2016)
  • Author(s): Oikawa Y, Morita KI, Kayamori K, Tanimoto K, Sakamoto K, Katoh H, Ishikawa S, Inazawa J, Harada H
  • Journal Title: Cancer Sci. Volume: 108 Issue: 2 Pages: 256-266
  • DOI: 10.1111/cas.13126
  • Peer Reviewed / Open Access
• [Presentation] Genomically defined Environmental and Germline Factors for Asian Gastric Cancer. (2020)
  • Author(s): Shumpei Ishikawa
  • Organizer: The 79th Annual Meeting of the Japanese Cancer Association
• [Presentation] 胃がんのシングルセル解析 (2020)
  • Author(s): 加藤洋人, 河村大輔, 坪坂歩, 古久保宙希, & 石川俊平.
  • Organizer: 第９１回日本衛生学会学術総会
• [Presentation] 環境要因とがん発生におけるゲノム変異シグネチャとの関連. (2020)
  • Author(s): 加藤洋人, 鈴木章浩, 河村大輔, 牛久哲男, 油谷浩幸, & 石川俊平.
  • Organizer: 第９１回日本衛生学会学術総会
• [Presentation] ゲノムから見たアジア人の胃がん. (2020)
  • Author(s): 石川俊平
  • Organizer: 第９１回日本衛生学会学術総会
• [Presentation] 肉腫患者由来ゼノグラフトのRNA発現解析. (2020)
  • Author(s): 大津敬, 笠島理加, 鷲見公太, 廣島幸彦, 片山琴絵, 清水英悟, 山口類, 井元清哉, 宮野悟, 河村大輔, 石川俊平, 横瀬智之, 比留間徹, & 宮城洋平.
  • Organizer: The 79th Annual Meeting of the Japanese Cancer Association
• [Presentation] Human epididymis protein 4の発現が膵臓癌における抗癌剤耐性・予後不良に与える影響. (2020)
  • Author(s): 大熊遼太朗, 矢田英理香, 石川俊平, 河村大輔, 久保田祐太郎, 濱田和幸, 堀池篤, 安藤清宏, 鶴谷純司, 吉村清, 笹田哲朗, 村上雅彦, 瀧本雅文, 角田卓也, & 和田聡.
  • Organizer: The 79th Annual Meeting of the Japanese Cancer Association
• [Presentation] 一細胞解析によるがんの多様性の解明. (2020)
  • Author(s): 石川俊平
  • Organizer: 第24回 日本がん分子標的治療学会学術総会
• [Presentation] 凍結臨床試料を用いたシングルセルRNA-seq法の確立 (2019)
  • Author(s): 橋本至, 加藤洋人, 林周斗, 河村大輔, 大島貴, 利野靖, 益田宗孝, 石川俊平
  • Organizer: 第90回日本衛生学会学術総会（誌上開催）
• [Presentation] Single-cell analysis of diffuse-type gastric carcinoma microenvironment (2019)
  • Author(s): Shumpei Ishikawa
  • Organizer: 第78回日本癌学会学術総会
• [Presentation] The genomic profile of metastatic diffuse-type gastric cancer in Cdh1loxP/loxP; Trp53loxP/loxP double conditional knockout mice (2019)
  • Author(s): Zhang, Menghua, Sugita, Itsuki, Komura, Daisuke, Ishikawa, Shumpei
  • Organizer: 第42回 日本分子生物学会年会
• [Presentation] Visualizing ligand-receptor-mediated interactome in single cell transcriptome data (2019)
  • Author(s): Daisuke Komura, Ryohei Suzuki, Shumpei Ishikawa
  • Organizer: Cold Spring Harbor Laboratory Meeting, Systems Immunology
  • Int'l Joint Research
• [Presentation] Interactome analysis of gastric cancer microenvironment by single-cell transcriptome sequencing (2019)
  • Author(s): Shumpei Ishikawa, Daisuke Komura, Ryohei Suzuki, Hiroto Katoh
  • Organizer: Cell Symbosia. Single Cells: Technology to Biology
  • Int'l Joint Research
• [Presentation] Comprehensive and serial analyses of tumor-stroma interactions in individual PDX/NOG models contribute to personalized chemotherapy. (2017)
  • Author(s): T. Chijiwa, M. Haraguchi, D. Komura, A. Noguchi, M. Shiozawa, M. Katayama, N. Miyao, N. Matsui, Y. Tateishi, H. Suemizu, Y. Nakamura, T. Isagawa, H. Katoh, S. Ishikawa, M. Nakamura, Y. Miyagi
  • Organizer: AACR International Conference on New Frontiers in Cancer Research
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2017-01-18
  • Int'l Joint Research
• [Presentation] 治療標的探索のためのがんー間質細胞間相互作用の網羅的解析. (2017)
  • Author(s): 河村大輔, 鈴木良平, 加藤洋人, 山本尚吾, 油谷浩幸, 石川俊平.
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] CASTIN: a system for comprehensive analysis of cancer-stromal interactome. (2017)
  • Author(s): Daisuke Komura, Takayuki Isagawa, Ryohei Suzuki, Reiko Sato, Mariko Tanaka, Shogo Yamamoto, Masashi Fukayama, Hiroyuki Aburatani, Shumpei Ishikawa.
  • Organizer: The 12th International Workshop on Advanced Genomics
  • Int'l Joint Research
• [Presentation] 治療標的探索のためのがん－間質細胞間相互作用解析システム. (2017)
  • Author(s): 河村大輔, 砂河孝行, 鈴木良平, 佐藤玲子, 加藤洋人, 田中麻理子, 山本尚吾, 深山正久, 油谷浩幸, 石川俊平.
  • Organizer: 第106回 日本病理学会総会
• [Presentation] Establishment of patient-derived xenografts from malignant pleural effusion using NOG mice. (2016)
  • Author(s): Chijiwa, M. Haraguchi, T. Isagawa, A. Noguchi, M. Katayama, N. Miyao, M. Yoshioka, N. Matsui, Y. Tateishi, H. Suemizu, R. Yamada, Y. Nakamura, K. Imai, D. Komura, H. Katoh, S. Ishikawa, M. Nakamura, Y. Miyagi.
  • Organizer: ESMO Asia 2016 Congress
  • Place of Presentation: Singapore, Singapore
  • Year and Date: 2016-12-16
  • Int'l Joint Research
• [Presentation] 腫瘍ー間質間相互作用解析システム. (2016)
  • Author(s): 河村大輔, 砂河孝行, 鈴木良平, 貴志一樹, 佐藤玲子, 加藤洋人, 田中麻里子, 山本尚吾, 深山正久, 油谷浩幸, 石川俊平
  • Organizer: 第75 回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜市、神奈川県
• [Presentation] 肺腺癌Xenograft モデルにおける癌間質相互作用の包括的解析. (2016)
  • Author(s): 吉本多一郎, 松原大祐, 仁木利郎, 河村大輔, 石川俊平.
  • Organizer: 第75 回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜市、神奈川県
• [Remarks]
  • URL: http://www.tmd.ac.jp/gpat/index.html