Elucidation of tumor microenvironment formation mechanism in metastatic lesion using new metastatic renal carcinoma model and its application to therapy

• Project/Area Number: 15K20105
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: National Cancer Center Japan (2016); Osaka City University (2015)
• Principal Investigator: Yamano Shotaro 国立研究開発法人国立がん研究センター, 研究所, 特任研究員 (80614528)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肺転移 / 癌細胞塊 / 腎細胞癌 / 高転移株 / クラスター

Outline of Final Research Achievements

Tumor microenvironment formation is one of the most critical event for cancer metastasis and malignancy. previously we generated the novel metastatic model of renal cancer using rat renal cell carcinoma cell line rRCCd5 which are established by us. In this study, we generated the highly lung metastatic clones of rRCCd5 via in vivo selection method, and underwent the phenotype screening of metastatic clones in vivo and in vitro and transcriptome analyses. These analyses revealed that over-expressions of protein X and Y in the highly metastatic clones might contribute to accelerate the lung metastasis ability via facilitating the cancer cluster formation by cancer cell adhesion dys-regulation.
Further study are needed for understanding the relationship between the protein X or Y and tumor microenvironment formation in the lung metastatic lesions of renal cancers.

Research Products

• [Journal Article] Carbonic anhydrase 2 is a novel invasion-associated factor in urinary bladder cancers. (2017)
  • Author(s): Tachibana H, Gi M, Kato M, Yamano S, Fujioka M, Kakehashi A, Hirayama Y, Koyama Y, Tamada S, Nakatani T, Wanibuchi H.
  • Journal Title: Cancer Sci Volume: 108 Issue: 3 Pages: 331-337
  • DOI: 10.1111/cas.13143
  • Peer Reviewed / Open Access
• [Journal Article] Diphenylarsinic acid exerts promotion effects on hepatobiliary carcinogenesis in a rat medium-term multiorgan carcinogenicity bioassay (2017)
  • Author(s): Ishii N, Gi M, Fujioka M, Yamano S, Okumura M, Kakehashi A, Wanibuchi H.
  • Journal Title: Journal of Toxicologic Pathology Volume: 30 Issue: 1 Pages: 39-45
  • DOI: 10.1293/tox.2016-0049
  • NAID: 130005297205
  • ISSN: 0914-9198, 1881-915X
  • Peer Reviewed / Open Access
• [Journal Article] A chronic toxicity study of diphenylarsinic acid in F344 rats in drinking water for 52 weeks. (2017)
  • Author(s): Yamaguchi T, Gi M, Yamano S, Fujioka M, Tatsumi K, Kawachi S, Ishii N, Doi K, Kakehashi A, Wanibuchi H.
  • Journal Title: Exp Toxicol Pathol Volume: 69 Issue: 1 Pages: 1-7
  • DOI: 10.1016/j.etp.2016.10.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Anti-PD-L1 treatment enhances antitumor effect of everolimus in a mouse model of renal cell carcinoma. (2016)
  • Author(s): Hirayama Y, Gi M, Yamano S, Tachibana H, Okuno T, Tamada S, Nakatani T, Wanibuchi H.
  • Journal Title: Cancer Sci Volume: 107 Issue: 12 Pages: 1736-1744
  • DOI: 10.1111/cas.13099
  • Peer Reviewed / Open Access
• [Journal Article] Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway. (2016)
  • Author(s): Inaba H, Goto H, Kasahara K, Kumamoto K, Yonemura S, Inoko A, Yamano S, Wanibuchi H, He D, Goshima N, Kiyono T, Hirotsune S, Inagaki M.
  • Journal Title: J Cell Biol. Volume: 212 Issue: 4 Pages: 409-423
  • DOI: 10.1083/jcb.201507046
  • Peer Reviewed / Open Access
• [Journal Article] The role of deltaNp63pos CD44vpos cells in the development of NTCU-induced peripheral type of mouse lung squamous cell carcinomas.. (2016)
  • Author(s): Yamano S, Gi M, Tago Y, Doi K, Okada S, Hirayama S, Tachibana H, Ishii N, Fujioka M, Tatsumi K,Wanibuchi H.
  • Journal Title: Cancer Sci Volume: 107 Issue: 2 Pages: 123-132
  • DOI: 10.1111/cas.12855
  • Peer Reviewed / Open Access
• [Presentation] p53標的遺伝子IER5は新規の低リン酸化型の活性化HSF1を作り出し、がん化を促進する (2017)
  • Author(s): 山野荘太郎
  • Organizer: 第11回 臨床ストレス応答学会
  • Place of Presentation: 山口大学医学部（山口県宇部市）
  • Year and Date: 2017-11-11
• [Presentation] ラット腎癌肺高転移株を用いた転移亢進に寄与するCAMsに関する検討 (2016)
  • Author(s): 山野荘太郎
  • Organizer: 第25回日本がん転移学会学術総会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2016-07-21