Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor

Kazuki Nabeshima, Teruhiko Inoue, Yoshiya Shimao, Yasunori Okada, Yoshifumi Itoh, Motoharu Seiki, Masashi Koono

研究成果: Article

108 引用 (Scopus)

抄録

Migration of tumor cells is usually assessed as single cell locomotion in vitro using Boyden chamber type assays. In vivo, however, carcinoma cells frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement 'cohort migration' and developed a two-dimensional in vitro cohort migration model, in which human rectal well-differentiated adenocarcinoma cells (L-10) migrate from piled-up cell islands as coherent sheets of cells when stimulated with hepatocyte growth factor/scatter factor. In this study, we examined whether there is a cohort migration-specific way of expression of matrix metalloproteinases (MMP) and whether degradation of extracellular matrix is necessary for this type of migration. Production of membrane-type 1-MMP (MT1-MMP) and gelatinase A (MMP- 2) by L-10 cells was demonstrated by gelatin zymography, immunoblotting, and reverse transcription-PCR. When cohort migration was induced with hepatocyte growth factor/scatter factor, MT1-MMP and MMP-2 were immunolocalized predominantly in the leading edges of the front cells of migrating cell sheets, with the following cells being negative. In addition, during the cohort migration on gelatin-coated substratum, the gelatin matrix was degraded by the cells, in a very organized manner, causing radially arrayed lysis of gelatin matrix at the sites of leading edges. BB94, a synthetic inhibitor specific to MMPs, tissue inhibitor of metalloproteinases-1 and -2, and the COOH-terminal hemopexin-like domain of MMP-2 inhibited the migration on gelatin matrix. Thus, these data demonstrate that gelatin matrix is reorganized to suit cell migration via leading-edge-of-front-cell-specific localization of MT1-MMP and MMP-2 during cohort migration and suggest that the reorganization is essential for this type of migration.

元の言語English
ページ(範囲)3364-3369
ページ数6
ジャーナルCancer Research
60
発行部数13
出版物ステータスPublished - 2000 7 1

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Matrix Metalloproteinase 14
Hepatocyte Growth Factor
Matrix Metalloproteinase 2
Colon
Carcinoma
Gelatin
Matrix Metalloproteinases
Cell Movement
Hemopexin
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Immunoblotting
Reverse Transcription
Extracellular Matrix
Adenocarcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

これを引用

Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor. / Nabeshima, Kazuki; Inoue, Teruhiko; Shimao, Yoshiya; Okada, Yasunori; Itoh, Yoshifumi; Seiki, Motoharu; Koono, Masashi.

:: Cancer Research, 巻 60, 番号 13, 01.07.2000, p. 3364-3369.

研究成果: Article

Nabeshima, Kazuki ; Inoue, Teruhiko ; Shimao, Yoshiya ; Okada, Yasunori ; Itoh, Yoshifumi ; Seiki, Motoharu ; Koono, Masashi. / Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor. :: Cancer Research. 2000 ; 巻 60, 番号 13. pp. 3364-3369.
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abstract = "Migration of tumor cells is usually assessed as single cell locomotion in vitro using Boyden chamber type assays. In vivo, however, carcinoma cells frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement 'cohort migration' and developed a two-dimensional in vitro cohort migration model, in which human rectal well-differentiated adenocarcinoma cells (L-10) migrate from piled-up cell islands as coherent sheets of cells when stimulated with hepatocyte growth factor/scatter factor. In this study, we examined whether there is a cohort migration-specific way of expression of matrix metalloproteinases (MMP) and whether degradation of extracellular matrix is necessary for this type of migration. Production of membrane-type 1-MMP (MT1-MMP) and gelatinase A (MMP- 2) by L-10 cells was demonstrated by gelatin zymography, immunoblotting, and reverse transcription-PCR. When cohort migration was induced with hepatocyte growth factor/scatter factor, MT1-MMP and MMP-2 were immunolocalized predominantly in the leading edges of the front cells of migrating cell sheets, with the following cells being negative. In addition, during the cohort migration on gelatin-coated substratum, the gelatin matrix was degraded by the cells, in a very organized manner, causing radially arrayed lysis of gelatin matrix at the sites of leading edges. BB94, a synthetic inhibitor specific to MMPs, tissue inhibitor of metalloproteinases-1 and -2, and the COOH-terminal hemopexin-like domain of MMP-2 inhibited the migration on gelatin matrix. Thus, these data demonstrate that gelatin matrix is reorganized to suit cell migration via leading-edge-of-front-cell-specific localization of MT1-MMP and MMP-2 during cohort migration and suggest that the reorganization is essential for this type of migration.",
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T1 - Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor

AU - Nabeshima, Kazuki

AU - Inoue, Teruhiko

AU - Shimao, Yoshiya

AU - Okada, Yasunori

AU - Itoh, Yoshifumi

AU - Seiki, Motoharu

AU - Koono, Masashi

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N2 - Migration of tumor cells is usually assessed as single cell locomotion in vitro using Boyden chamber type assays. In vivo, however, carcinoma cells frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement 'cohort migration' and developed a two-dimensional in vitro cohort migration model, in which human rectal well-differentiated adenocarcinoma cells (L-10) migrate from piled-up cell islands as coherent sheets of cells when stimulated with hepatocyte growth factor/scatter factor. In this study, we examined whether there is a cohort migration-specific way of expression of matrix metalloproteinases (MMP) and whether degradation of extracellular matrix is necessary for this type of migration. Production of membrane-type 1-MMP (MT1-MMP) and gelatinase A (MMP- 2) by L-10 cells was demonstrated by gelatin zymography, immunoblotting, and reverse transcription-PCR. When cohort migration was induced with hepatocyte growth factor/scatter factor, MT1-MMP and MMP-2 were immunolocalized predominantly in the leading edges of the front cells of migrating cell sheets, with the following cells being negative. In addition, during the cohort migration on gelatin-coated substratum, the gelatin matrix was degraded by the cells, in a very organized manner, causing radially arrayed lysis of gelatin matrix at the sites of leading edges. BB94, a synthetic inhibitor specific to MMPs, tissue inhibitor of metalloproteinases-1 and -2, and the COOH-terminal hemopexin-like domain of MMP-2 inhibited the migration on gelatin matrix. Thus, these data demonstrate that gelatin matrix is reorganized to suit cell migration via leading-edge-of-front-cell-specific localization of MT1-MMP and MMP-2 during cohort migration and suggest that the reorganization is essential for this type of migration.

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