Single cell interactome analysis for the discovery of targets to overcome anti-cancer drug resistance.

• Project/Area Number: 17H04992
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Medical genome science
• Research Institution: The University of Tokyo (2018-2019); Tokyo Medical and Dental University (2017)
• Principal Investigator: Komura Daisuke 東京大学, 大学院医学系研究科(医学部), 助教 (10776082)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000); Fiscal Year 2019: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000); Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: がん / 治療標的 / ゲノム / がん-間質細胞間相互作用 / シングルセルトランスクリプトーム / がん間質相互作用 / 癌

Outline of Final Research Achievements

From single-cell transcriptome data of tumor tissues, we developed a method to analyze and visualize the entire cell-cell interaction (interactome) between various cells such as cancer cells, fibroblasts, immune cells, and vascular endothelial cells. Using this method, we performed interactome analysis of single-cell transcriptome data of normal gastric mucosa and gastric cancer tissues from human samples, and gastric cancer tissues from the mouse model of diffuse-type gastric cancer. The results suggest that signals from various cells, including fibroblasts, may contribute to the progression of cancer. These included molecules that have been reported to be associated with attenuated effects of anticancer drugs.

Academic Significance and Societal Importance of the Research Achievements

がん細胞は通常それ単独では生存できず、周囲のさまざまな細胞と相互作用することによって生存に有利な状況を作り出している。近年組織における遺伝子発現量を一細胞レベルで定量化する技術が開発された。本研究ではこのデータを用いてがん細胞と周囲の非がん細胞との間の相互作用を定量化・可視化する技術を開発した。本手法をマウスのがん組織やヒトの正常組織、がん組織に適用したところ、正常組織からがん組織に至る過程で重要な相互作用を明らかにした。また、その中には抗がん剤の効果を弱める可能性のある分子も含まれていた。本研究成果をさらに進めることでがんの本体解明や抗癌剤耐性獲得の機序解明などにつながることが期待される。

Research Products

• [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] High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer. (2020)
  • Author(s): Ohkuma R, Yada E, Ishikawa S, Komura D, Ishizaki H, Tamada K, Kubota Y, Hamada K, Ishida H, Hirasawa Y, Ariizumi H, Satoh E, Shida M, Watanabe M, Onoue R, Ando K, Tsurutani J, Yoshimura K, Yokobori T, Sasada T, Aoki T, Murakami M, Norose T, Ohike N, Takimoto M, Izumizaki M, Kobayashi S, Tsunoda T, Wada S.
  • Journal Title: PLoS One Volume: 10 Issue: 1 Pages: e0226707-e0226707
  • DOI: 10.1371/journal.pone.0226707
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The genomic profile of metastatic diffuse-type gastric cancer in Cdh1loxP/loxP; Trp53loxP/loxP double conditional knockout mice (2020)
  • Author(s): Menghua Zhang, Itsuki Sugita, Daisuke Komura, Shunpei Ishikawa
  • Organizer: 第90回 日本衛生学会学術総会
• [Presentation] Single-cell transcriptomics of a model mouse for diffuse-type gastric cancer reveal ligand-receptor interactions potentially important for the cancer development (2020)
  • Author(s): 古久保宙希、河村大輔、加藤洋人、石川俊平
  • Organizer: 第20回 東京大学生命科学シンポジウム
• [Presentation] The genomic profile of metastatic diffuse-type gastric cancer in Cdh1loxP/loxP; Trp53loxP/loxP double conditional knockout mice (2019)
  • Author(s): Menghua Zhang, Itsuki Sugita, Daisuke Komura, Shunpei Ishikawa
  • Organizer: 第42回 日本分子生物学会年会
• [Presentation] 膵癌における包括的癌-間質インタラクトーム解析 (2019)
  • Author(s): 廣島, 幸彦; 笠島, 理加; 木村, 弥生; 河村, 大輔; 石川, 俊平; 市川, 靖史; 遠藤, 格; 宮城, 洋平
  • Organizer: 日本癌学会学術総会
• [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] Single cell analysis for the human gastric cancer environments (2017)
  • Author(s): Hiroto Katoh, Daisuke Komura, Shumpei Ishikawa.
  • Organizer: Cold Spring Harbor Laboratory Meeting, Single Cell Analyses
  • 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
• [Book] 遺伝統計学と疾患ゲノムデータ解析 : 病態解明から個別化医療, ゲノム創薬まで (2018)
  • Author(s): 岡田 随象(編集)、河村大輔ら
  • Total Pages: 264
  • Publisher: メディカルドゥ
  • ISBN: 9784944157631
• [Book] 遺伝統計学と疾患ゲノムデータ解析 (2018)
  • Author(s): 岡田随象(編集)、河村大輔、石川俊平ら
  • Total Pages: 272
  • Publisher: メディカルドゥ
  • ISBN: 4944157630