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Analysis of mechanisms involved in cohort migration of human colon carcinoma cells

Research Project

Project/Area Number 10670212
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionMiyazaki Medical College

Principal Investigator

NABESHIMA Kazuki  Miyazaki Medical College, Department of Pathology Associate Professor, 医学部, 助教授 (40189189)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordscancer / invasion / migration / HGF / SF / small G protein / E-cadherin / catenin complex / MMP / fibronectin / E∞cadherin / cell-cell contact / TGF-β1
Research Abstract

(I) Mechanisms of localized release from cell-cell adhesion during cohort migration
During cohort migration (CM) induced by hepatocyte growth factor/scatter factor (HGF/SF), migrating cells show localized release from cell-cell adhesion in the lower portion of the cells. This enables cells to extend leading edges and hence move. This localized release was associated with binding of IQGAP-1 to the E-cadherin/catenin complex. This caused release of α-catenin, which connects E-cadherin to actin filament cell skeleton, from the complex. This mechanism is now under investigation more in detail using dominant active/negative Rac 1 or cdc42-transfected cells.
(ii) Enhanced induction of cohort migration of carcinoma cells in the co-presence of fibroblasts
We made in vitro CM assays which are more similar to the in vivo situation by coculturing carcinoma cells with fibroblasts. Coexistence of fibroblasts enhanced HGF/SF-induced CM of carcinoma cells. In the coculture, carcinoma cells stimulated secretion of TGF-β1 by fibroblasts, and the increased TGF-β1 induced more production of motility-stimulating EDA-containing fibronectin by cells. Thus, cell-cell interaction is shown to play an important role in CM..
(iii) Front-cell-specific expression of matrix metalloproteinases (MMP) during cohort migration
During HGF/SF-induced CM, gelatinase A (GelA) and membrane type-1 matrix metalloproteinase (MT1-MMP) were positively demonstrated predominantly in front cells of the migrating sheets, with the following cells being negative. These MMPs caused rearrangement of gelatin matrix, which was essential for CM. Since the above front-cell-specific expression pattern of MMPs was effaced when scattering (single cell locomotion) of cells was induced instead of CM, cell-cell contact in migrating cell sheets appeared responsive for the pattern.

Report

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

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Y. Shimao, K. Nabeshima et al.: "Role of fibroblasts in HGF/SF-induced cohort migration of human colorectal carcinoma cells : fibroblasts stimulate migration associated with increased fibronectin production via upregulated TGF-β1"Int. J. Cancer. 82. 449-458 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Nabeshima et al.: "Cohort migration of carcinoma cells : Differentiated colorectal carcinoma cells move as coherent cell clusters or sheets"Histol. Histopathol.. 14. 1183-1197 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 鍋島一樹 他: "消化器癌の転移と細胞運動"Frontiers in Gastroenterology. 4. 385-394 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 鍋島一樹 他: "癌細胞浸潤能とMMP"現代医療. 32(4)(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Nabeshima et al.: "Front-cell-specifui expression of membrane-type 1 matrix metalloproteinase (MTI-MMP) and gelatinase A (MMP-2) during cohort migration of colon carcinoma cells induced by hepatocyte growth factoe/scatter factor (HGF/SF)"Cancer Res.. (being reviced).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Nabeshima et al.: "Cohort migration of carcinoma cells: Differentiated colorectal carcinoma cells move as coherent cell clusters or sheets."Histology and Histopathology. 14. 1183-1197 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Shimao, K. Nabeshima et al.: "Role of fibroblasts in HGF/SF-induced cohort migration of human colorectal carcinoma cells: fibroblasts stimulate migration associated with increased fibronectin production via upregulated TGF-β1"Int. J. Cancer. 82. 449-458 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Nabeshima et al.: "Metastasis of GI tract cancer cell motility"Frontiers in Gastroenterology and. 4. 385-394 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Nabeshima et al.: "Invasive ability of carcinoma cells and MMP"Gendai Iryo. 32(4) (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Nabeshima et al.: "Front-cell-specific expression of membrane-type 1 matrix metalloproteinase(MT1-MMP) and gelatinase A (MMP-2) during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor (HGF/SF)"Cancer Res.. (being revised).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Shimao,K.Nabeshima et al.: "Role of fibroblasts in HGF/SF-induced cohort migration of human colorectal carcinoma cells: fibroblasts stimulate migration associated with increased fibronectin production via upregulated TGF-β1"Int.J.Cancer. 82. 449-458 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Nabeshima et al.: "Cohort migration of carcinoma cells: Differentiated colorectal carcinoma cells-move as choherent cell clusters or sheets"Histol.Histopathol.. 14. 1183-1197 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鍋島一樹 他: "消化器癌の転移と細胞運動"Frontiers in Gastroenterology. 4. 385-394 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鍋島一樹 他: "癌細胞浸潤能とMMP"現代医療. 32(4)(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Nabeshima et al.: "Front-cell-specific exprssion of membrane-type 1 matrix metalloproteinase(MT1-MMP) and gelatinase A(MMP-2) during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor (HGF/SF)"Cancer Res.. being revised.

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Shimao,K.Nabeshima et al.: "Role of fibroblasts in HGF/SF-induced cohort migration of human colorectal carcinoma cells: fibroblasts stimulate migration associated with increased fibronectin production via upregulated TGF-β1" Int.J.Cancer. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Nabeshima et al.: "Cohort migration of carcinoma cells: Differentiated colorectal carcinoma cells move as coherent cell clusters or sheets" Histol.Histopathol.(in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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