Analysis of mechanical stress in lung cancer cells for therapeutic target search

• Project/Area Number: 15K09216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Fujita Health University (2017); Nagoya University (2015-2016)
• Principal Investigator: Kondo Masashi 藤田保健衛生大学, 医学部, 教授 (00378077)
• Co-Investigator(Kenkyū-buntansha): 伊藤 理 愛知医科大学, 医学部, 准教授 (60378073) ; 佐藤 光夫 名古屋大学, 医学部附属病院, 准教授 (70467281)
• Research Collaborator: Miyazawa Ayako
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肺癌 / メカノバイオロジー

Outline of Final Research Achievements

Cancer cells have a specific response to the physical force from the surroundings. Physical stimuli such as stretch stimulation and changes in matrix stiffness were applied to lung cancer cell lines and its effect on cell proliferation and molecular expression was examined. As the matrix stiffness decreased, expression of PD-L1 decreased and cell proliferation was suppressed. From pharmacological experiments, it was due to an actin-dependent mechanism. it was suggested that the physical microenvironment of the tumor such as matrix stiffness, is also involved in the regulation of tumor immunity.

Research Products

• [Journal Article] Regulation of PD-L1 expression by matrix stiffness in lung cancer cells (2018)
  • Author(s): Miyazawa Ayako、Ito Satoru、Asano Shuichi、Tanaka Ichidai、Sato Mitsuo、Kondo Masashi、Hasegawa Yoshinori
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 495 Issue: 3 Pages: 2344-2349
  • DOI: 10.1016/j.bbrc.2017.12.115
  • Peer Reviewed / Open Access
• [Journal Article] eIF2β, a Subunit of Translation-Initiation Factor EIF2, Is a Potential Therapeutic Target for Non-Small Cell Lung Cancer (2018)
  • Author(s): Tanaka Ichidai、Sato Mitsuo、Kato Toshio、Goto Daiki、Kakumu Tomohiko、Miyazawa Ayako、Yogo Naoyuki、Hase Tetsunari、Morise Masahiro、Sekido Yoshitaka、Girard Luc、Minna John D.、Byers Lauren A.、Heymach John V.、Coombes Kevin R.、Kondo Masashi、Hasegawa Yoshinori
  • Journal Title: Cancer Science Volume: - Issue: 6 Pages: 1843-1852
  • DOI: 10.1111/cas.13602
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of Proteasomal Catalytic Subunit PSMA6 as a Therapeutic Target for Lung Cancer. (2017)
  • Author(s): Kakumu T, Sato M, Goto D, Kato T, Yogo N, Hase T, Morise M, Fukui T, Yokoi K, Sekido Y, Girard L, Minna JD, Byers LA, Heymach JV, Coombes KR, Kondo M, Hasegawa Y.
  • Journal Title: Cancer Sci. Volume: 108 Issue: 4 Pages: 732-743
  • DOI: 10.1111/cas.13185
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phase II Study of Carboplatin and Pemetrexed in Advanced EGFR-wild-type Non-squamous Non-small Cell Lung Cancer: The Central Japan Lung Study Group Trial 0906. (2016)
  • Author(s): Kimura T, Taniguchi H, Watanabe N, Saka H, Kogure Y, Shindo J, Ogasawara T, Kojima E, Hasegawa Y, Yamamoto M, Suzuki R, Ando M, Kondo M, Saito H
  • Journal Title: Anticancer Res. Volume: 36(4) Pages: 1767-71
  • Peer Reviewed
• [Journal Article] Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells. (2015)
  • Author(s): Yamashita R, Sato M, Kakumu T, Hase, T, Yogo, N, Maruyama E, Sekido Y, Kondo M, Hasegawa, Y.
  • Journal Title: Cancer Medicine Volume: 4 Issue: 4 Pages: 551-564
  • DOI: 10.1002/cam4.412
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 翻訳開始因子Eurokaryotic initiation factor 2 subunit 2(EIF2S2)は非小細胞肺癌細胞株の増殖を抑制する (2016)
  • Author(s): 加藤俊夫 佐藤光夫,與語直之,;長谷哲成, 森瀬昌宏, 後藤大輝, 宮澤亜矢子, 近藤征史,長谷川好規
  • Organizer: 日本肺癌学会
  • Place of Presentation: 福岡国際会議場（福岡県、博多市）
  • Year and Date: 2016-12-19
• [Presentation] Cytochrome c oxidase subunit 5a (COX5A) is identified as a potential therapeutic target for lung cancer with high therapeutic index through a pooled shRNA screen (2016)
  • Author(s): Kato T, Sato M, Kondo M, Goto , Kato T, Kakumu T, Yogo N, Hase, Morise M, Fukui T, Girard L, Minna JD, Hasegawa Y
  • Organizer: アメリカ癌学会
  • Place of Presentation: ニューオリンズ、アメリカ
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] Cytochrome c oxidase subunit 5a (COX5A) is identified as a potential therapeutic target for lung cancer with high therapeutic index through a pooled shRNA screen (2016)
  • Author(s): Toshio Kato, Mitsuo Sato, Masashi Kondo, Tomohiko Kakumu, Naoyuki Yogo, Tetsunari Hase, Masahiro Morise, Yoshionori Hasegawa, John D. Minnna, Luc Girard.
  • Organizer: AACR Annual Meeting 2016
  • Place of Presentation: New Orleans,USa
  • Year and Date: 2016-04-16