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Analysis of the function of TM4SF complex and its application of lung cancer therapy.

Research Project

Project/Area Number 16390400
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionThe Tazuke Kofukai

Principal Investigator

MIYAKE Masayuki  The Tazuke Kofukai, Kitano Hospital The Tazuke Kofukai Medical Research Institute. The Fifth Department of Oncology, Department of Thoracic Surgery, Director, Associate-Director, 医学研究所第5研究部, 部長 (90250076)

Co-Investigator(Kenkyū-buntansha) HATTORI Noboru  Hiroshima University, Graduate School of Biomedical Sciences, Department of Molecular and Internal Medicine, Associate Professor, 大学院・医歯薬学総合研究科第2内科, 講師 (00283169)
HIROTA Kiichi  Kyoto University, Graduate School of Medicine, Department of Anesthesia, Associate Professor, 医学研究科麻酔科, 講師 (00283606)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥8,200,000 (Direct Cost: ¥8,200,000)
KeywordsTM4SF / AAH / MRP-1 / CD9 / KAI1 / CD82 / PETA3 / CD151 / 下位遺伝子 / MRP1 / VEGF-A
Research Abstract

Previously, we found that MRP-1/CD9, a member of the tetraspanin family, suppressed cell motility and metastatic potential to lungs. Moreover, reduction of MRP-1/CD9 gene expression was found to be a factor of a poor prognosis for the patients with non-small cell lung cancer, as was another member of TM4SF, KAI1/CD82. On the other hand, CD151 is identical to an exciting gene PETA-3 which may promote tumor metastasis of malignant cells and its expression may be involved in the malignant progression cancer. We have established various stages of lung cancer cell lines and investigated the complex between tetraspsnin family members and integrin family members. Especially, the complex formation of MRP-1/CD9, KAI1/CD82 and PETA3/CD151 were analyzed. In the Stage I, MRP-1/CD9 and KAI1/CD82 expression were found in two cell lines except one, but PETA3/CD151 appeared weak expression. In the Stage II, KAI1/CD82 was decreasing in 5 cases and MRP-1/CD9 was decreasing in 1 case, however PETA3/CD151 was increasing in 2 cases. In the StageIII, only KAI1/CD82was found decreasing in 4 cases. Then only PETA3/CD151 was appeared in the last 1case. In the StageIV, expression of PETA3/CD151 was positive in almost all metastatic cell lines. From these experiments, MRP-1/CD9 and KAI1/CD82 play an important role as metastasis suppressor genes. On the other hand, PETA3/CD151 plays a metastasis promotion gene. Hence, the balance and unbalance of these expressions have something to do with the process of 'metastasis. Besides, we have found that MRP-1/CD9 and KAI1/CD82 regulate VEGF-A gene and Wnt-1 gene. In addition, we have established the monoclonal antibody recognizing MRP-1/CD9-integrin α3 complex. Using this antibody, we will be able to analyze the mechanism of this complex.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (38 results)

All 2005 2004 Other

All Journal Article (34 results) Book (4 results)

  • [Journal Article] 細胞運動の制御による癌転移の抑制 Suppression of metastasis by inhibition of cell motility2005

    • Author(s)
      徳原孝洋, 三宅正幸
    • Journal Title

      外科治療 93

      Pages: 221-222

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Circulating aminopeptidase N/CD13 is an independent prognostic factor inpatients with non-small cellIung cancer.2005

    • Author(s)
      Murakami, H. et al.
    • Journal Title

      Clin. Cancer Res. 11

      Pages: 8674-8679

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Two cases of hyperkalemia after administration of hypertonic mannitol during craniotomy.2005

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      J. Anesth. 19

      Pages: 75-77

    • NAID

      10014429030

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases.2005

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 338

      Pages: 610-616

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia reduces constitutive and TNF-alpha-induced Expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells.2005

    • Author(s)
      Li, X.et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 335

      Pages: 1026-1034

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] KL-6, a human MUC1 mucin. promotes proliferation and survival of lung fibroblasts.2005

    • Author(s)
      Ohshimo, S. et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 30

      Pages: 1845-1852

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Circulating aminopeptidase N/CD13 is an independent prognostic factor in patients with non-small cell lung cancer2005

    • Author(s)
      Murakami, H., Yokoyama, A., Kondo, K., Nakanishi, S., Kohno, N., Miyake, M.
    • Journal Title

      Clin.Cancer Res 11

      Pages: 8674-8679

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Two cases of hyperkalemia after administration of hypertonic mannitol during craniotomy.2005

    • Author(s)
      Hirota, K., Hara, T., Hosoi, S., Hara, Y., Adachi, T.
    • Journal Title

      J.Anesth. 19

      Pages: 75-77

    • NAID

      10014429030

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases.2005

    • Author(s)
      Hirota, K., Semenza, G.
    • Journal Title

      Biochem.Biophys.Res.Commun 338

      Pages: 610-606

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia reduces constitutive and TNF-alpha-induced expression of Monocyte chemoattractant protein-1 in human proximal renal tubular cells.2005

    • Author(s)
      Li, X., Kimura, H., Hirota, K., Sugimoto, H., Yoshida, H.
    • Journal Title

      Biochem.Biophys.Res.Commun 335

      Pages: 1026-1034

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] KL-6, a human NUC1 mucin, promotes proliferation and survival of Lung fibroblasts.2005

    • Author(s)
      Ohshimo, S., Yokoyama, A., Hattori, N., Ishikawa, N., Hirasawa, Y., Kohno, N.
    • Journal Title

      Biochem.Biophys.Res.Commun 30

      Pages: 1845-1852

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Circulating aminopeptidase N/CD13 is an independent prognostic factor in patients with non-small celllung cancer.2005

    • Author(s)
      Murakami, H. et al.
    • Journal Title

      Clin.Cancer Res. 11

      Pages: 8674-8679

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinicopathological significance of Aminopeptidase N/CD13 expression in human gastric carcinoma.2005

    • Author(s)
      Kawamura, J. et al.
    • Journal Title

      Hepato-gastroenterol. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Two cases of hyperkalemia after administration of hypertonic mannitol during craniotomy.2005

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      J.Anesth. 19

      Pages: 75-77

    • NAID

      10014429030

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases.2005

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 338

      Pages: 610-616

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypoxia reduces constitutive and TNF-alpha-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells.2005

    • Author(s)
      Li, X.et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 335

      Pages: 1026-1034

    • Related Report
      2005 Annual Research Report
  • [Journal Article] KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts.2005

    • Author(s)
      Ohshimo, S. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 30

      Pages: 1845-1852

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The Plasminogen activation system reduces fibrosis in the lung by a Hepatocyte growth factor-dependent mechanism.2004

    • Author(s)
      Hattori, N., et al.
    • Journal Title

      Am. J. Pathol. 164

      Pages: 1091-1098

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MRP-1/CD9 gene transduction downregulates Wnt signal pathways.2004

    • Author(s)
      Huang, C. et al.
    • Journal Title

      Oncogene 23

      Pages: 7475-7483

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 癌の封じ込めによる肺切除適応の拡大 Enlargement of application for lung cancer surgery based on metastasis prevention.2004

    • Author(s)
      石田久雄 et al.
    • Journal Title

      外科治療 90

      Pages: 85-86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 多変量解析による膵癌の進展・予後に関与する遺伝子異常の検索2004

    • Author(s)
      池田直也 et al.
    • Journal Title

      病理と臨床 22

      Pages: 819-825

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Plasminogen activation system reduces fibrosis in the lung by a Hepatocyte growth factor-dependent mechanism.2004

    • Author(s)
      Hattori, N., Mizuno, S., Yoshida, Y., Chin, K., Mishima, M., Sisson, TH., Simon, RH., Nakamura, T., Miyake, M.
    • Journal Title

      Am.J.Pathol. 164

      Pages: 1091-1098

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene therapy for pulmonary diseases.2004

    • Author(s)
      Hattori, N., Miyake, M.
    • Journal Title

      Frontiers in Immuno-gene Therapy

      Pages: 209-225

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MRP-1/CD9 gene transduction downregulates Wnt signal pathways.2004

    • Author(s)
      Huang, C., Liu, D., Masuya, D., Kameyama, K., Nakashima, T., Yokomise, H., Ueno, M., Miyake, M.
    • Journal Title

      Oncogene 23

      Pages: 7475-7483

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism.2004

    • Author(s)
      Hattori, N. et al.
    • Journal Title

      American Journal of Pathology 164

      Pages: 1091-1098

    • Related Report
      2004 Annual Research Report
  • [Journal Article] MRP-1/CD9 gene transduction downregulates Wnt signal patyhways.2004

    • Author(s)
      Huang, C. et al.
    • Journal Title

      Oncogene 23

      Pages: 7475-7483

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Response shift in perception of sleepiness in obstructive sleep apnea-hyppnea syndrome before and after treatment with nasal CPAP.2004

    • Author(s)
      Chin, K. et al.
    • Journal Title

      Sleep 27

      Pages: 490-493

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The intravenous anesthetic propofol inhibits hypoxia-inducible factor 1 activity in an oxgen thesion-dependent manner.2004

    • Author(s)
      Takabuchi, S. et al.
    • Journal Title

      FEBS Lett 577

      Pages: 434-438

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The inhibitory effect of sodium nitroprusside on HIF-1 activation is not dependent on nitric oxide-soluble guanylyl cyclase pathway.2004

    • Author(s)
      Takabuchi, S. et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 324

      Pages: 417-423

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of hypoxia-inducible factor 1 activity by muscarinic acetylcholine receptor signaling.2004

    • Author(s)
      Hirota, K. et al.
    • Journal Title

      Journal of Biological Chemistry 279

      Pages: 41521-41528

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinical significance of Aminopeptidase N in Non-Small Cell LungCancer.

    • Author(s)
      Tokuhara, T. et al.
    • Journal Title

      Clin. Cancer Res. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MRP-1/CD9 gene transduction ragulates the actin cytoskelet on through the down-regulation of WAVE2.

    • Author(s)
      Huang, CL. et al.
    • Journal Title

      Oncogene (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MRP-1/CD9 gene transduction regulates the actin cytoskeleton throug the down-regulation of WAVE2.

    • Author(s)
      Huang, CL., Ueno, M., Liu, D., Masuya, D., Nakano, J., Yokomise, H., Nakagawa, T., Miyake, M.
    • Journal Title

      Oncogene (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Clinical significance of Aminopeptidase N in Non-Small Cell LungCancer.

    • Author(s)
      Tokuhara, T., Hattori, N., Ishida, H., Hirai, T., Higashiyama, M., Kodama, K., Miyake, M.
    • Journal Title

      Clin, Cancer, Res. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 呼吸器外科の最新医療2005

    • Author(s)
      石田久雄, 三宅正幸
    • Total Pages
      3
    • Publisher
      先端医療技術研究所
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 外科治療2005

    • Author(s)
      徳原孝洋, 三宅正幸
    • Total Pages
      2
    • Publisher
      永井書店
    • Related Report
      2005 Annual Research Report
  • [Book] Frontiers in Immuno-gene Therapy2004

    • Author(s)
      Hattori, N., Miyake, M.
    • Total Pages
      16
    • Publisher
      Research Signpost
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Frontiers in Immuno-gene Therapy2004

    • Author(s)
      Hattori, N., Miyake, M.
    • Total Pages
      16
    • Publisher
      Osamu Mazda
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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