Development of CTC-detection system for thoracic malignant tumors

• Project/Area Number: 16K10697
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: TANAKA FUMIHIRO 産業医科大学, 医学部, 教授 (10283673)
• Co-Investigator(Kenkyū-buntansha): 米田 和恵 産業医科大学, 医学部, 助教 (80724806)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 転移 / 循環腫瘍細胞 / 肺癌 / 中皮腫 / マイクロ流路 / 微小転移 / CTC-chip / 胸膜中皮腫 / 癌

Outline of Final Research Achievements

Detection and control of micrometastases are necessary to improve treatment outcomes of patients with malignant tumors. We had tried to detect rare tumor cells that circulate in the peripheral blood (circulating tumor cells, CTCs), and developed a micro-fluidic system (CTC-chip) that could be conjugated with any antibody to capture tumor cells. In the present study, we modified the CTC-chip system to optimize conditions for detection of CTCs in clinical samples, and successfully achieved a sensitive detection of CTCs in experimental studies using cell lines. Next, we tested the performance to detect CTCs in peripheral blood sampled from patients with lung cancer and malignant pleural mesothelioma, and revealed that the CTC-chip system achieved a significant higher CTC-detection performance than the CellSearch system that was most frequently employed CTC-detection system.

Academic Significance and Societal Importance of the Research Achievements

本研究によりがん患者の末梢血液中に存在する微量ながん細胞を高感度に検出するシステムが開発され、採血という侵襲の少ない検査によりがんの早期発見の可能性が開かれた。また検出されたがん細胞の遺伝子変異などの分子生物学的特性を調べることも可能であり、これに基づいた最適の治療、特に標的薬剤や免疫チェックポイント阻害剤などの新規薬剤、の選択が可能となると期待される。またがんの微小転移や生物学的特性の変化をリアルタイムにモニタリングが可能になることから、新たながんの生物学的特性や転移のメカニズムの解明とこれに基づく新薬開発につながると期待される。

Research Products

• [Journal Article] Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma (2019)
  • Author(s): Yoneda K, Kuwata T, Chikaishi Y, Mori M, Kanayama M, Takenaka M, Oka S, Hirai A, Imanishi N, Kuroda K, Ichiki Y, Ohnaga T, Tanaka F.
  • Journal Title: Cancer Science Volume: 110 Issue: 2 Pages: 726-733
  • DOI: 10.1111/cas.13895
  • Peer Reviewed / Open Access
• [Journal Article] A liquid biopsy in primary lung cancer (2019)
  • Author(s): Yoneda K, Imanishi N, Ichiki Y, Tanaka F.
  • Journal Title: Surgical Today Volume: 49 Issue: 1 Pages: 1563-1569
  • DOI: 10.1007/s00595-018-1659-2
  • Peer Reviewed
• [Journal Article] The clinical value of circulating tumour cells (CTCs) in patients undergoing pulmonary metastasectomy for metastatic colorectal cancer. (2018)
  • Author(s): Hashimoto M, Tanaka F, Yoneda K, Takuwa T, Kuroda A, Matsumoto S, Okumura Y, Kondo N, Tsujimura T, Nakano T, Hasegawa S.
  • Journal Title: J Thorac Dis. Volume: 10 Issue: 3 Pages: 1569-1577
  • DOI: 10.21037/jtd.2018.03.05
  • Peer Reviewed / Open Access
• [Journal Article] Programmed death-ligand 1 (PD-L1) expression in pleomorphic carcinoma of the lung (2018)
  • Author(s): Imanishi N, Hirai A, Yoneda K, Shimajiri S, Kuwata T, Tashima Y, Takeuchi M, Iwai Y, Ichiki Y, Tanaka F.
  • Journal Title: Journal of Surgical Oncology Volume: 117 Issue: 7 Pages: 1563-1569
  • DOI: 10.1002/jso.25041
  • Peer Reviewed
• [Journal Article] Capture of mesothelioma cells with 'universal' CTC-chip. (2018)
  • Author(s): Yoneda K, Chikaishi Y, Kuwata T, Ohnaga T, Tanaka F
  • Journal Title: Oncology Letters Volume: 5(2) Pages: 2635-2640
  • DOI: 10.3892/ol.2017.7619
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic impact of programmed death-ligand 1 expression in correlation with human leukocyte antigen class I expression status in stage I adenocarcinoma of the lung. (2018)
  • Author(s): Hirai A, Yoneda K, Shimajiri S, Kuroda K, Hanagiri T, Fujino Y, Tanaka F.
  • Journal Title: J Thorac Cardiovasc Surg. Volume: 155 Issue: 1 Pages: 382-392
  • DOI: 10.1016/j.jtcvs.2017.05.106
  • Peer Reviewed / Open Access
• [Journal Article] EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip' (2017)
  • Author(s): Chikaishi Y, Yoneda K, Ohnaga T, Tanaka F
  • Journal Title: ONCOLOGY REPORTS Volume: 37.1 Issue: 1 Pages: 77-82
  • DOI: 10.3892/or.2016.5235
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Circulating Tumor Cells as an Indicator of Postoperative Lung Cancer: A Case Report. (2017)
  • Author(s): Kuwata T, Yoneda K, Kobayashi K, Oyama R, Matumiya H, Shinohara S, Takenaka M, Oka S, Chikaishi Y, Inanishi N, Kuroda K, Tanaka F.
  • Journal Title: The American Journal of Case Reports Volume: 17 Pages: 663-665
  • DOI: 10.12659/ajcr.898934
  • Peer Reviewed
• [Journal Article] Circulating Tumor Cells: A Novel Detection System with “Universal” CTC-chip. (2016)
  • Author(s): Yoneda K, Tanaka F.
  • Journal Title: Proceedings of World Automation Congress Volume: - Pages: 631-634
  • Peer Reviewed
• [Presentation] 呼吸器悪性腫瘍におけるLiquid Biopsy (2018)
  • Author(s): 米田和恵、桒田泰治、近石泰弘、大永 崇、田中文啓
  • Organizer: 第2回Liquid Biopsy研究会
• [Presentation] Capture of tumor cells in blood with “Universal CTC-chip”. (2017)
  • Author(s): Kazue Yoneda, Taiji Kuwata, Yasuhiro Chikaishi, Fumihiro Tanaka.
  • Organizer: 24th International Molecular Med TRI-CON
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2017-02-19
  • Int'l Joint Research
• [Presentation] Universal CTC-chipによる血液中腫瘍細胞の捕捉 (2017)
  • Author(s): 米田和恵、桒田泰治、近石泰弘、由良冴希子、小林健一、小山倫太郎、松宮弘喜、金山雅俊、平良彰浩、名部裕介、篠原伸二、竹中 賢、岡 壮一、平井文子、田嶋裕子、今西直子、黒田耕志、大永 崇、田中文啓
  • Organizer: 第1回Liquid Biopsy研究会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2017-01-21
• [Presentation] “Universal CTC-chip”による血液中腫瘍細胞の捕捉と検出に関する基礎検討 (2017)
  • Author(s): 米田和恵、桒田泰治、近石泰弘、大永 崇、田中文啓
  • Organizer: 第35回日本ヒト細胞学会学術集会
• [Presentation] “Universal CTC-Chip”と抗ポドプラニン抗体NZ-1を用いた中皮腫細胞の捕捉 (2017)
  • Author(s): 米田和恵、加藤幸成、田中文啓
  • Organizer: 第21回がん分子標的治療学会
• [Presentation] Detection of CTCs in thoracic malignant tumors with "universal" CTC-chip. (2017)
  • Author(s): Kazue Yoneda, Taiji Kuwata, Yasuhiro Chikaishi, Kenichi Kobayashi , Sakiko Yura, Hiroki Matsumiya, Masatoshi Kanayama, Akihiro Taira, Yusuke Nabe, Shinji Shinohara, Masaru Takenaka, Soichi Oka, Ayako Hirai, Yuko Tashima, Naoko Imanishi, Koji Kuroda, Fumihiro Tanaka
  • Organizer: America Association for Cancer Research (AACR) Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] Sensitive Detection of CTCs in Thoracic Malignant Tumors with "Universal" CTC-Chip. (2016)
  • Author(s): Yoneda K, Kuwata T, Chikaishi Y, Kobayashi K, Oyama R, Yura S, Matsumiya H, Taira A, Nabe Y, Takenaka M, Oka S, Hirai A, Tashima Y, Imanishi N, Kuroda K, Ohnaga T, Tanaka F.
  • Organizer: IASLC 17th World Conference on Lung Cancer.
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2016-12-06
  • Int'l Joint Research
• [Presentation] “Universal CTC-chip”を用いた血液中腫瘍細胞の捕捉 (2016)
  • Author(s): 米田和恵、大永 崇、田中文啓
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-07
• [Presentation] “Universal CTC-chip”による血液中の中皮腫細胞捕捉 (2016)
  • Author(s): 米田和恵、桒田泰治、近石泰弘、由良冴希子、小林健一、小山倫太郎、松宮弘喜、平良彰浩、名部裕介、竹中 賢、岡 壮一、平井文子、田嶋裕子、今西直子、黒田耕志、田中文啓
  • Organizer: 第7回JMIG研究会
  • Place of Presentation: JPタワー名古屋ホール＆カンファランス（愛知県名古屋市）
  • Year and Date: 2016-09-03
• [Presentation] Circulating Tumor Cells: A Novel Detection System with “Universal” CTC-chip. (2016)
  • Author(s): Kazue Yoneda, Fumihiro Tanaka.
  • Organizer: World Automation Congress 2016 Japan Satellite Session
  • Place of Presentation: Himeji, Japan
  • Year and Date: 2016-08-07
  • Int'l Joint Research
• [Presentation] “Universal CTC-chip”による血液中腫瘍細胞の捕捉 (2016)
  • Author(s): 米田和恵 近石泰弘、田中文啓
  • Organizer: 第1回CTC臨床応用研究会
  • Place of Presentation: 東大寺総合文化センター（奈良県奈良市）
  • Year and Date: 2016-07-17