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Microenviroment and organ specific metastases in urological cancers as tools to elucidate molecular mechanism of carcinogenesis and tumor development.

Research Project

Project/Area Number 21390445
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKeio University

Principal Investigator

OYA Mototsugu  慶應義塾大学, 医学部, 教授 (00213885)

Co-Investigator(Kenkyū-buntansha) MIKAMI Syuuji  慶應義塾大学, 医学部, 助教 (20338180)
NAKAGAWA Ken  慶應義塾大学, 医学部, 准教授 (50227740)
MIYAJIMA Akira  慶應義塾大学, 医学部, 講師 (90245572)
KIKUCHI Eiji  慶應義塾大学, 医学部, 講師 (10286552)
小坂 威雄  慶應義塾大学, 医学部, 研究員(非常勤) (30445407)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2011: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2009: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords腎細胞癌 / 分子標的治療 / 上皮-間葉転換 / Snail / 転移 / 浸潤 / E-cadherin / 骨転移 / RANKL / RANK
Research Abstract

Ninety-seven primary(renal cell carcinomas) RCCs were analyzed for the protein expression of Snail, Slug, MMP2 and MMP9 by immunohistochemistry. Snail protein expression level was positively correlated with pathological tumor stage, histological grade and the presence of sarcomatoid carcinoma. Because Snail was positively associated with malignant potential of RCCs, involvement of Snail in the invasiveness of an RCC cell lines 786-O and ACHN were examined in the Matrigel invasion assay by down-regulating the gene expression with small interfering RNA(siRNA). Invasion of the cells through Matrigel in vitro was inhibited under this condition. Furthermore, expression levels of MMP2 and MMP9 were positively correlated with pathological tumor stage and the presence of sarcomatoid carcinoma. In conclusion, these data suggest that Snail has an important role in invasion and metastasis, and that silencing the gene may be a potenal therapeutic target in RCCs.
Receptor activator of NF-κB ligand(RANKL) and its receptor, receptor activator of NF-κB(RANK), play a key role in osteoclastogenesis RANKL protein expression level showed positive correlations with the primary tumour stage and distant metastasis. RANKL and RANK expression was observed in metastatic RCCs in the bone and other organs, suggesting that they play a role in metastasis to the bone and other organs. Recombinant RANKL protein stimulated migration of a clear cell RCC cell line, Caki-1, in vitro, and this enhanced migration was inhibited by the administration of recombinant OPG protein. These data suggest that the RANKL-RANK-OPG system is involved not only in the bone metastasis of RCCs but also in metastasis to other organs through the stimulation of cancer cell migration.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (18 results)

All 2012 2011 2010 2009 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (5 results) Remarks (3 results)

  • [Journal Article] Patterns of Interstitial Lung Disease During Everolimus Treatment in Patients with Metastatic Renal Cell Carcinoma2012

    • Author(s)
      Mizuno R, Asano K, Oya M, et al.
    • Journal Title

      Jpn J Clin Oncol

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Patterns of Interstitial Lung Disease During Everolimus Treatment in Patients with Metastatic Renal Cell Carcinoma2012

    • Author(s)
      Mizuno R, Asano K, Oya M, et al
    • Journal Title

      Jpn J Clin Oncol

      Volume: (Epub)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Snail and Slug in renal cell carcinoma : E-cadherin repressor Snail is associated with cancer invasion and prognosis2011

    • Author(s)
      Mikami S, Katsube K, Oya M, et al.
    • Journal Title

      Lab Invest

      Volume: 91(10) Pages: 1443-58

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of the Aryl hydrocarbon receptor pathway enhances cancer cell invasion by up-regulating the MMP expression and is associated with poor prognosis in upper urinary tract urothelial cancer.2010

    • Author(s)
      Ishida M, Mikami S, Kikuchi E, Kosaka T, Miyajima A, Nakagawa K, Mukai M, Okada Y, Oya M
    • Journal Title

      Carcinogenesis

      Volume: 31(2) Pages: 287-295

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cis-dichlorodiammineplatinum upregulates angiotensin II type 1 receptors through reactive oxygen species generation and enhances VEGF production in bladder cancer.2010

    • Author(s)
      Tanaka N, Miyajima A, Kosaka T, Shirotake S, Hasegawa M, Kikuchi E, Oya M.
    • Journal Title

      Mol Cancer Ther

      Volume: 9(11) Pages: 2982-2992

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Snail in upper urinary tract urothelial carcinoma : Prognostic significance and implications for tumor invasion.2010

    • Author(s)
      Kosaka T, Kikuchi E, Mikami S, Miyajima A, Shirotake S, Ishida M, Okada Y, Oya M
    • Journal Title

      Clin Cancer Res

      Volume: 16(23) Pages: 5814-5823

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ets-1 and hypoxia inducible factor-lalpha inhibition by angiotensin II type-1 receptoe blockade in hormone-refractory prostate cancer2010

    • Author(s)
      Kosaka T, et al
    • Journal Title

      Prostate 70(2)

      Pages: 162-169

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas2009

    • Author(s)
      Mikami S, Katsube K, Oya M, et al.
    • Journal Title

      J Pathol

      Volume: 218(4) Pages: 530-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased RANKL expression is related to tumour migration and metast asis of renal cell carcinomas2009

    • Author(s)
      Mikami S, et al
    • Journal Title

      J Pathol 218

      Pages: 530-539

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preoperative prognostic nomogram(probabilitytable)for renal cell carcinoma based on TNM classifiration2009

    • Author(s)
      Kanao K, et al
    • Journal Title

      J Urol 181(2)

      Pages: 480-485

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] High nuclear grade has strong prognostic significance in patients with pathologic T1a renal cell carcinoma2012

    • Author(s)
      Suzuki K, Oya M, et al.
    • Organizer
      27th Annual EAU Congress
    • Place of Presentation
      Paris
    • Year and Date
      2012-02-27
    • Related Report
      2011 Final Research Report
  • [Presentation] High nuclear grade has strong prognostic significance in patients with pathologic T1a renal cell carcinoma2012

    • Author(s)
      Suzuki K, Oya M, et al
    • Organizer
      27th Annual EAU Congress
    • Place of Presentation
      Paris, France
    • Year and Date
      2012-02-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Expression of E-cadherin repressor Snail in renal cell carcinoma : Implication for cancer invasion and prognosis2011

    • Author(s)
      Oya M, Mikami S, et al.
    • Organizer
      22nd Urological Research Society Conference
    • Place of Presentation
      Oxford
    • Year and Date
      2011-09-24
    • Related Report
      2011 Final Research Report
  • [Presentation] Activation of the aryl hydrocarbon receptor is associated with cigarette smoke, poor prognosis and cancer cell invasion in renal cell carcinoma.2010

    • Author(s)
      Ishida M., Mikami S., Kosaka T., Kono H., Kikuchi E., Nagata H., Miyajima A., Nakagawa K., Mukai M., Okada Y., Oya M.
    • Organizer
      25^<th> Anniversary Congress of the European Association of Urology
    • Place of Presentation
      Barcelona
    • Year and Date
      2010-04-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] 転移性腎癌治療の現状と将来展望2009

    • Author(s)
      大家基嗣
    • Organizer
      第47回日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Remarks] 泌尿器科学教室ホームページ

    • URL

      http://www.keio-urology.jp

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.keio-urology.jp/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.keio-urology.jp/indox.html

    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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