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Prediction of cancer metastasis by tumor endothelial secreting proteins

Research Project

Project/Area Number 26462390
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionHokkaido University

Principal Investigator

Shinohara Nobuo  北海道大学, 医学研究科, 教授 (90250422)

Co-Investigator(Kenkyū-buntansha) 間石 奈湖  北海道大学, 遺伝子病制御研究所, 助教 (00632423)
土屋 邦彦  北海道大学, 大学病院, 助教 (50374442)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords腫瘍血管新生 / biglycan / 転移 / 腫瘍血管内皮 / biglycan, / LOX / biglycan, LOX
Outline of Final Research Achievements

In this study, we addressed the involvement of tumor endothelial secreting molecule in cancer metastasis. Among these molecules, we focused on biglycan and analyzed the role of biglycan in cancer metastatic potential. We observed that biglycan-secreted from tumor endothelial cells activate NF-B and ERK in cancer cells and attract cancer cells towards tumor blood vessels, resulting in increase of lung metastasis. Furthermore, blood level of biglycan in cancer patients correlated with vascular invasion of cancer. These suggested that tumor endothelial secreting factor may be biomarker in cancer metastasis.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (37 results)

All 2017 2016 2015 2014

All Journal Article (29 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 27 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Vasohibin-1 as a novel prognostic factor for head and neck squamous cell carcinoma2017

    • Author(s)
      Torii C., Hida Y., Shindoh M., Akiyama K., Ohga N., Maishi N., Ohiro Y., Ono M., Totsuka Y., Kitagawa Y., Tei K., Sato Y., Hida K.
    • Journal Title

      Anticancer Res

      Volume: 37 Issue: 3 Pages: 1219-1225

    • DOI

      10.21873/anticanres.11437

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aneuploidy of murine immortalized endothelial cell line, MS1.2017

    • Author(s)
      Hida K., Maishi N., Dorcas Akuba-Muhyia Annan, Kondoh M., Hojo T., Umma Habiba, Ohga N., Ishikawa K, Sato M., Torii C., Yanagiya M., Morimoto M., Hida Y., Shindoh M.
    • Journal Title

      J Oral Biosci

      Volume: 59 Issue: 1 Pages: 50-54

    • DOI

      10.1016/j.job.2016.10.004

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aldo-keto reductase 1C1 induced by interleukin-1beta mediates the invasive potential and drug resistance of metastatic bladder cancer cells.2016

    • Author(s)
      Matsumoto R, Tsuda M, Yoshida K, Tanino M, Kimura T, Nishihara H, Abe T, Shinohara N, Nonomura K, Tanaka S
    • Journal Title

      Scientific reports

      Volume: 4 Issue: 1 Pages: 34625-34625

    • DOI

      10.1038/srep34625

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Outcome of metastatic urothelial carcinoma treated by systemic chemotherapy: Prognostic factors based on real-world clinical practice in Japan.2016

    • Author(s)
      Abe T, Ishizaki J, Kikuchi H, Minami K, Matsumoto R, Harabayashi T, Sazawa A, Mochizuki T, Chiba S, Akino T, Murakumo M, Miyajima N, Tsuchiya K, Maruyama S, Murai S, Shinohara N.
    • Journal Title

      Urologic oncology

      Volume: 35 Issue: 2 Pages: 38.e1-38.e8

    • DOI

      10.1016/j.urolonc.2016.08.016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor endothelial cells express high pentraxin 3 levels2016

    • Author(s)
      Hida K., Maishi N., Kawamoto T., Akiyama K., Ohga N., Hida Y., Yamada K., Hojo T., Kikuchi H., Sato M., Torii C., Shinohara N., Shindoh M
    • Journal Title

      Pathol Int

      Volume: 66 Issue: 12 Pages: 687-694

    • DOI

      10.1111/pin.12474

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of characteristics of mouse immortalized normal endothelial cells, MS1 and primary cultured endothelial cells.2016

    • Author(s)
      Hida K., Maishi N., Torii C., Yanagiya M., Annan Akuba-Muhyia Dorcas., Morimoto M., Alam Mohammad Towfik
    • Journal Title

      Hokkaido J. Dent. Sci.

      Volume: 37 Pages: 40-48

    • NAID

      120005855959

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan.2016

    • Author(s)
      N. Maishi, Y. Ohba, K. Akiyama, N. Ohga, J.I. Hamada, H. Nagao-Kitamoto, M. Alam, K. Yamamoto, T. Kawamoto, N. Inoue, A. Taketomi, M. Shindoh, Y. Hida and K. Hida.
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 28039-28039

    • DOI

      10.1038/srep28039

    • NAID

      120005819304

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Five-point Likert scaling on MRI predicts clinically significant prostate carcinoma.2015

    • Author(s)
      Harada T, Abe T, Kato F, Matsumoto R, Fujita H, Murai S, Miyajima N, Tsuchiya K, Maruyama S, Kudo K, Shinohara N
    • Journal Title

      BMC urol

      Volume: 91

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma.2015

    • Author(s)
      Hotta K, Sho M, Fujimoto K, Shimada K, Yamato I, Anai S, Harada H, Tsujikawa K, Konishi N, Shinohara N, Nakajima Y
    • Journal Title

      Oncol reports

      Volume: 34 Pages: 648-654

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of a subgroup with worse prognosis among patients with poor-risk testicular germ cell tumor.2015

    • Author(s)
      Kojima T, Kawai K, Tsuchiya K, Abe T, Shinohara N, Tanaka T, Masumori N, Yamada S, Arai Y, Narita S, Tsuchiya N, Habuchi T, Nishiyama H
    • Journal Title

      Int J Urol

      Volume: 22 Issue: 10 Pages: 923-927

    • DOI

      10.1111/iju.12844

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prospective mapping of lymph node metastasis in Japanese patients undergoing radical cystectomy for bladder cancer: characteristics of micrometastasis.2015

    • Author(s)
      Matsumoto R, Takada N, Abe T, Minami K, Harabayashi T, Nagamori S, Hatanaka KC, Miyajima N, Tsuchiya K, Maruyama S, Murai S, Shinohara N
    • Journal Title

      Jpn. J. Clin. Oncol

      Volume: 45 Pages: 874-880

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] CRK adaptor protein induces epithelial-mesenchymal transition and metastasis of bladder cancer cells via HGF/c-Met feedback loop.2015

    • Author(s)
      Matsumoto R, Tsuda M, Wang L, Maishi N, Abe T, Kimura T, Tanino M, Nishihara H, Hida K, Ohba Y, Shinohara N, Nonomura K, Tanaka S
    • Journal Title

      Cancer Sci

      Volume: 106 Pages: 709-717

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diagnostic outcome of ureteroscopy in urothelial carcinoma of the upper urinary tract: Incidence of later cancer detection and its risk factors after the first examination.2015

    • Author(s)
      Murahashi N, Abe T, Shinohara N, Murai S, Harabayashi T, Sazawa A, Maruyama S, Tsuchiya K, Miyajima N, Hatanaka K, Nonomura K
    • Journal Title

      BMC Urol

      Volume: 92 Issue: 1

    • DOI

      10.1186/s12894-015-0086-6

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phase 1/2 study of S-1 in combination with sorafenib for metastatic renal cell carcinoma.2015

    • Author(s)
      Naito S, Sakai H, Hashine K, Tomita T, Shinohara N, Fujisawa M, Eto M, Ozono S, Akaza H
    • Journal Title

      Ann Oncol

      Volume: 26 Pages: 1871-1876

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognosis of Japanese patients with previously untreated metastatic renal cell carcinoma in the era of molecular-targeted therapy.2015

    • Author(s)
      Shinohara N, Obara W, Tatsugami K, Naito S, Kamba T, Takahashi M, Murai S, Abe T, Oba K, Naito S
    • Journal Title

      Cancer Sci

      Volume: 106 Pages: 618-626

    • NAID

      120005619614

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Japanese Society of Renal Cancer: Role of cytoreductive nephrectomy for Japanese patients with primary renal cell carcinoma in the cytokine and targeted therapy era.2015

    • Author(s)
      Tatsugami K, Shinohara N, Kondo T, Yamasaki T, Eto M, Tsushima T, Terachi T, Naito S
    • Journal Title

      Int J Urol

      Volume: 22 Pages: 736-740

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] CXCL 12-CXCR7 axis is important for tumor endothelial cell angiogenic property2015

    • Author(s)
      Yamada K., Maishi N., Akiyama K., Alam Mohammad Towfik, Ohga N., Kawamoto T., Shindoh M. Takahashi N., Kamiyama T., Hida Y., Taketomi A. and Hida K.
    • Journal Title

      Int J Cancer

      Volume: 137 Pages: 2825-2836

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of multidrug transporter in tumor endothelial cells enhances antiangiogenic effects of low-dose metronomic paclitaxel2015

    • Author(s)
      Akiyama K., Maishi N., Ohga N., Hida Y., Ohba Y., Alam Mohammad Towfik, Kawamoto T., Ohmura H., Yamada K., Torii C., Shindoh M. and *Hida K.
    • Journal Title

      Am J Pathol

      Volume: 185 Pages: 572-580

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] CRK adaptor protein induces epithelial-mesenchymal transition and metastasis of bladder cancer cells via HGF/c-Met feedback loop2015

    • Author(s)
      Matsumoto R, Tsuda M, Wang L, et al
    • Journal Title

      Cancer science

      Volume: in press

    • Related Report
      2014 Research-status Report
  • [Journal Article] Prognosis of Japanese patients with previously untreated metastatic renal cell carcinoma in the era of molecular-targeted therapy2015

    • Author(s)
      Shinohara N, Obara W, Tatsugami K et al
    • Journal Title

      Cancer science

      Volume: in press

    • NAID

      120005619614

    • Related Report
      2014 Research-status Report
  • [Journal Article] Outcome of metastasectomy for urothelial carcinoma: a multi-institutional retrospective study in Japan2014

    • Author(s)
      Abe T, Kitamura H, Obara W, Matsumura N, Tsukamoto T, Fujioka T, Hara I, Murai S, Shinohara N, Nonomura K
    • Journal Title

      The Journal of urology

      Volume: 191 Pages: 932-936

    • NAID

      120005438267

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of 90-day complications between ileal conduit and neobladder reconstruction after radical cystectomy: A retrospective multi-institutional study in Japan2014

    • Author(s)
      Abe T, Takada N, Shinohara N, Matsumoto R, Murai S, Sazawa A, Maruyama S, Tsuchiya K, Kanzaki S, Nonomura K
    • Journal Title

      International journal of urology

      Volume: 21 Pages: 554-559

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful penile reconstruction after multimodal therapy in patients with primitive neuroectodermal tumor originating from the penis2014

    • Author(s)
      Akino T, Shinohara N, Hatanaka K, Kobayashi N, Yamamoto Y, Nonomura K
    • Journal Title

      International journal of urology

      Volume: 21 Pages: 619-621

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification and expression of troponin T, a new marker on the surface of cultured tumor endothelial cells by aptamer ligand2014

    • Author(s)
      Ara MN, Hyodo M, Ohga N, Akiyama K, Hida K, Hida Y, Shinohara N, Harashima H
    • Journal Title

      Cancer medicine

      Volume: 3 Pages: 825-834

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] RENAL nephrometry score is a predictive factor for the annual growth rate of renal mass2014

    • Author(s)
      Matsumoto R, Abe T, Shinohara N, Murai S, Maruyama S, Tsuchiya K, Nonomura K
    • Journal Title

      International journal of urology

      Volume: 21 Pages: 549-552

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells2014

    • Author(s)
      Otsubo T, Hida Y, Ohga N, Sato H, Kai T, Matsuki Y, Takasu H, Akiyama K, Maishi N, Kawamoto T, Shinohara N, Nonomura K, Hida K
    • Journal Title

      Cancer science

      Volume: 105 Pages: 560-567

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suprabasin as a novel tumor endothelial cell marker2014

    • Author(s)
      Alam MT, Nagao-Kitamoto H, Ohga N, Akiyama K, Maishi N, Kawamoto T, Shinohara N, Taketomi A, Shindoh M, Hida Y et al
    • Journal Title

      Cancer science

      Volume: 105 Pages: 1533-1540

    • NAID

      120005539218

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Overall survival and final efficacy and safety results from a Japanese phase Ⅱstudy of axitinib in cytokine-refractory metastatic cell carcinoma2014

    • Author(s)
      Eto M, Uemura H, Tomita Y, Hanayama H, Shinohara N, Kamei Y, Fujii Y, Umeyama Y, Ozono S, Naito S et al
    • Journal Title

      Cancer science

      Volume: 105 Pages: 1576-1583

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suprabasin as a novel tumor endothelial cell marker2014

    • Author(s)
      Alam Mohammed Towfik, Nagao-Kitamoto H, Ohga N, Akiyama K, Maishi N, Kawamoto T, Shinohara N, Taketomi A, Shindoh M, Hida Y, Hida K
    • Journal Title

      Cancer Science

      Volume: 105 Pages: 1533-1540

    • NAID

      120005539218

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 腫瘍血管内皮細胞によるBiglycanの分泌を介したがんの転移促進2017

    • Author(s)
      間石奈湖
    • Organizer
      第2回口腔医科学フロンティア研究会
    • Place of Presentation
      ZAOセンタープラザ(山形市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Correlation between CXCR7 expression of blood vessels and clinicopathological features in oral squamous cell carcinoma,2016

    • Author(s)
      柳谷美沙,間石奈湖,鳥居ちさほ,樋田泰浩,大賀則孝,鄭 漢忠,進藤正信,北川善政,樋田京子
    • Organizer
      第24回日本血管生物医学会学術集会
    • Place of Presentation
      長崎ブリックホール(長崎市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Tumor endothelial cells acquire drug resistance by exosomal-miR derived from high metastatic tumor.2016

    • Author(s)
      Hida K., Torii C., Maishi N., Morimoto M., Akiyama K., Kawamoto T., Minami T., Yoshioka Y., Mohammad Towfik Alam, Shindoh M., Hida Y., Ochiya T
    • Organizer
      The 19th International Vascular Biology Meeting, 2016
    • Place of Presentation
      Sheraton Boston Hotel(Boston, US)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tumor endothelial cells in high metastatic tumors promote metastasis via biglycan2016

    • Author(s)
      Maishi N., Ohba Y., Akiyama K., Ohga N., Hamada J., Nagao-Kitamoto H., Mohammad Towfik Alam, Shindoh M., Hida Y. Hida K.
    • Organizer
      The 19th International Vascular Biology Meeting
    • Place of Presentation
      Sheraton Boston Hotel(Boston,US)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 「癌研究における女性研究者」,“腫瘍血管内皮細胞によるがん転移促進”2016

    • Author(s)
      間石奈湖,樋田京子
    • 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)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 「酸化ストレスと発がん~最新の知見~」,“活性酸素が腫瘍血管内皮細胞に及ぼす影響”2016

    • Author(s)
      間石 奈湖、樋田 京子
    • Organizer
      第 69 回日本酸化ストレス学会学術集会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 腫瘍血管内皮細胞によるbiglycanの分泌を介したがんの転移促進2016

    • Author(s)
      間石奈湖,秋山廣輔,大賀則孝,浜田淳一,樋田京子
    • Organizer
      第25回日本がん転移学会学術集会・総会
    • Place of Presentation
      米子コンベンションセンター(米子市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腫瘍血管内皮細胞によるがん転移促進2016

    • Author(s)
      間石奈湖
    • Organizer
      第12回北海道癌免疫制御研究会
    • Place of Presentation
      メルキュールホテル札幌(札幌市)
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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