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Study for Molecular Mechanisms of Endothelial and Methotelial Cell Retraction during Cancer Cell Invasion

Research Project

Project/Area Number 10671182
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionOsaka University

Principal Investigator

NAKAMORI Shoji  Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助手 (70294080)

Co-Investigator(Kenkyū-buntansha) DONO Keizo  Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助手 (60283769)
SAKON Masato  Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助教授 (40170659)
ARIYOSHI Hideo  Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助手 (60294055)
UMESHITA Kouji  Osaka University Hospital, Osaka University, Assistant Professot, 医学部・附属病院, 助手 (60252649)
NAGANO Hiroaki  Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助手 (10294050)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsInvasion / Endothelial cell / Retraction / FAK / Phosphorylation / Rho / Pancreatic Cancer / 癌転移 / 蛋白リン酸化 / 血管内皮細胞開裂 / pp125FAK
Research Abstract

When cancer cell permeates to the endothelial cell layer, endothelial cells should retract. We established assay system to measure quantitatively endothelial cell retraction activity and fonud that the endothelial cell retraction activity existed for human cancer cell culture supernatant over the 10 types using culture cell experimental system. Using pancreatic carcinoma cell line PSN-1 of which the endothelial cell retraction activity is the strongest, mechanisms of signal transduction during the endothelial cell retraction was examined. Addition of conditioned medium (CM) of PSN-1 cell culture induced decrease of phosphorylation of 120〜130Kd protein in the endothelial cell, and it was recognized that the protein with the decrease of phosphorylation is focal adhesion kinase that is involved in the intracellular skeleton control. To examine involvement of change of intracellular calcium level in the decrease of phosphorylation of 120〜130Kd protein, we observed intracellular calcium level in the endothelial cells by the confocal laser microscope. Addition of CM did not induced any change of intracellular calcium level in the endothelial cells. However, the change of intracellular calcium levels in endothelial cells was increased soon after cancer cell attached on endothelial cells. It was also found that the increase of intracellular calcium level in the endothelial cell was generated in the several decades second interval. These findings suggested that the increase of intracellular calcium should play an important role in the endothelial cell retraction. We also examine the signal transduction during the invasion in the cancer cell side. We found that increased expression of Rho, which is one of the low molecular weight GTP binding protein, enhanced cancer cell invasion.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(31 results)

All Other

All Publications (31 results)

  • [Publications] Nakamori S, et al.: "Increased blood proinsulin and decreased C-peptide levels in with pancreatic cancer"Hepato-Gastoroenterology. 46. 16-24 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamori S, et al.: "Morecular mechanism involved in increased expression of siayl lewis antigens in ductal carcinoma of the pnacreas"J Exp Clin Cancer Res. 18. 425-432 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshioka K, et al.: "Overexpression of small GTP-binding RhoA promotes invasion of tumar cells"Cancer Res. 59. 2004-2010 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwao K, et al.: "Activation of the β-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis colimutations"Cancer Res. 58. 1021-1026 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamoto H, et al.: "Down-regulation of facal adhesion kinase, pp125FAK, in endothelial cell retraction during timor cell invasion"Clin Exp Metastasis. 16. 243-252 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada T, et al.: "Detection of K-ras gene mutation in plasma DNA of patients with pancreatic adenocarcinoma : correlation with clinipathological features"Clin Cancer Res. 4. 1527-1532 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamori S., Ishikawa O., Ohigashi H., Sasakuma F., Shimizu T., Nakaizumi A., Furukawa H., Sasaki Y., Imaoka S.: "Increased blood proinsulin and decreased C-peptide levels in patients with pancreatic cancer.."Hepato-Gastroenterology. 46. 16-24 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamori S., Nishihara S., Ikehara Y., Nagano H., Dono K., Sakon M., Narimatsu H., Monden M.: "Molecular mechanism involved in increased expression of sialyl lewis antigens in ductal carcinoma of the pancreas."J Exp Clin Cancer Res. 18. 425-432 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwao K., Nakamori S., Kameyama M., Imaoka S., Kinoshita M., Fukui T., Ishiguro S., Nakamura Y., Miyoshi Y.: "Activation of the EィイD2τィエD2 catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations."Cancer Res. 58. 1021-1026 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okamoto H., Nakamori S., Mukai M., Shonkai K., Ohigashi H. Ishikawa O., Furukawa H., Imaoka S., Matsumoto Y., Monden M., Akedo H.: "Down-regulation of focal adhesion kinase, pp125FAK, in endothelial cell retraction during tumor cell invasion."Clin Exp Metastasis. 16. 243-252 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada T., Nakamori S., Ohzato H., Oshima S., Aoki T., Higaki N., Sugimoto K., Akagi K., Fujiwara Y., Nishisho I., Sakon M., Gotoh M., Monden M.: "Detection of K-ras Gene Mutations in Plasma DNA of Patients with Pancreatic Adenocarcinoma : Correlation with Clinicopathological Features."Clin Cancer Res. 4. 1527-1532 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Togayachi A., Kudo T., Ikehara Y., Iwasaki H., Nishihara S., Andoh T., Higashiyama M., Kodama K., Nakamori S., Narimatsu H.: "Up-regulation of Lewis enzyme (Fuc-TIII) and plasma-type Eφ, 3fucosyltransferase (Fuc-TVI) expression determines the augmented expression of sialyl Lewis X antigen in non-small cell lung cancer."Int J Cancer. 83. 70-79 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshioka K., Nakamori S., Itoh K: "Overexpression of small GTP-binding RhoA promotes invasion of tumor cells."Cancer Res. 59. 2004-2010 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakagawa H., Koyama K., Nakamori S., Kameyama M., Imaoka S., Monden M., Nakamura Y.: "Frameshift mutation of the STKII gene in a sporadic gastrointestinal cancer with microsatellite instability."Jpn J Cancer Res. 90. 633-637 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ariyoshi H., Okahara K., Sakon M., Kambayashi J., Kawashima S., Kawasaki T., Monden M.: "Possible involvement of m-Calpain in vascular smooth muscle cell proliferation"Arterioscler Thromb Vascular Biology. 18. 493-498 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda M., Ariyoshi H., Sakon M., Kambayashi J., Yoshikawa N., Shinoki N., Kawasaki T., Monden M.: "A role for local calcium gradients upon hypoxic injury in human umbilical vein endothelial cells (HUVEC)."Cell Calcium. 24. 49-57 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinoki N., Kawasaki T., Minamino N., Okahara K., Ogawa A., Ariyoshi H., Sakon M., Kambayashi J., Kangawa K., Monden M.: "Shear stress down-regulates gene transcription and production of adrenomedullin in human aortic endothelial cells."J Cell Biochem. 71. 109-115 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshikawa N., Ariyoshi H., Aono Y., Sakon M., Kawasaki T., Monden M: "Gradients in cytoplasmic calcium concentration ([Ca2+]i) in migrating human umbilical vein endothelial cells (HUVECs) stimulated by shear-stress.".Life Sciences. 65. 2643-2651 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito Y., Takeda T., Umeshita K., Sakon M., Wakasa K., Matsuura N., Monden M.: "Fas antigen expression in hepatocellular carcinoma tissues."Oncol Rep. 5. 41-44 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito Y., Matsuura N., Sakon M., Miyoshi E., Noda K., Takeda T., Umeshita K., Nagano H., Nakamori S., Dono K., Tsujimoto M., Nakahara M., Nakao K., Taniguchi N., Monden M: "Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma : p27 independently predicts the recurrence."Hepatology. 30. 90-99 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okami J., Yamamoto H., Fujiwara Y., Tsujie M., Kondo M., Noura S., Oshima S., Nagano H., Dono K., Umeshita K., Ishikawa O., Sakon M., Matsuura N., Nakamori S., Monden M.: "Overexpression of cyclooxy genase-2 in carcinoma of the pancreas."Clin Can Res. 5. 2018-2024 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiratsuka M., Furukawa H., Iwanaga T., Tamura S., Yasuda T., Nakamori S., Ohigashi H., Kameyama M., Sasaki Y., Kabuto T., Ishikawaed. O., Imaoka S.: "Peritoneal lavage cytology and intraperitoneall chemotherapy. in Peritoneal Dissemination-Molecular mechanisms and the latest therapy-.."Maeda Shoten, Kanazawa, ed. Yonemura Y.. 201-215 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamori S.et al.: "Increased blood proinsulin and decreased C-peptide levels in with pancreatic cancer"Hepato-Gastoroenterology. 46. 16-24 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamori S.et al.: "Morecular mechanism involved in increased expression of sialyl lewis antigens in ductal carcinoma of the pnacreas"J Exp Clin Cancer Res. 18. 425-432 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshioka K.et al.: "Overexpression of small GTP-binding RhoA promotes invasion of tumar cells"Cancer Res. 59. 2004-2010 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwao K.et al.: "Antivation of the β-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis colimutations"Cancer Res. 58. 1021-1026 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto H.et al: "Down-regulation of focal adhesion kinase, pp125FAK, in endothelial cell retraction during timor cell invasion"Clin EXP Metastasis. 16. 243-252 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamada T.et al.: "Detection of K-ras gene mutation in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinipathological features"Clin Cancer Res. 4. 1527-1532 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto H,et al.: "Down-regulation of focal adhesion kinase,pp125FAK,in endothelial cells retraction during tumor cell invasion." Clin Exp Metastasis. 16(3). 243-252 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshioka K,et al.: "Overexpression of small GTP-binding protein Rho promotes invasion of tumor cells." Cancer Res.in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] 中森正二: "浸潤・転移におけるシグナル伝達機構-内皮細胞開裂におけるシグナル伝達-" 実験医学. 6. 132-137 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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