Adhesive Defect in Extracellular Matrix Tenascin-X-Null Fibroblasts : A Possible Mechanism of Tumor Invasion
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概要
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Extracellular matrix tenascin-X (TNX)-null mice, generated by disruption of the Tnx gene, display augmented invasion and metastasis of B16-BL6 melanoma tumor cells due to increased activities of matrix metalloproteinase (MMP)-2 and MMP-9. In this study, we investigated cell-matrix and cell-cell adhesions using TNX-null fibroblasts and wild-type fibroblasts. TNX-null fibroblasts exhibited a decreased attachment to fibronectin compared with that of wild-type fibroblasts. B16 melanoma cells were cocultured with wild-type or TNX-null fibroblasts, and the adhesion of B16 melanoma to the fibroblasts was assessed. B16 melanoma cells on wild-type fibroblasts proliferated and spread out in a horizontal direction, whereas those on TNX-null fibroblasts overlapped each other rather than migrating horizontally. These overlapping B16 melanoma cells on TNX-null fibroblasts peeled off faster than those on wild-type fibroblasts. To determine whether the decreased cell-matrix and cell-cell adhesions on TNX-null fibroblasts were due to increased MMP activity, the activities of MMPs in wild-type and TNX-null fibroblasts were compared by gelatinolytic assays. The analysis of MMPs from conditioned media demonstrated that almost the same levels of MMP activities were detected between wild-type and TNX-null fibroblasts. However, contrary to our expectations the activities of MMPs from conditioned media of B16 melanoma cells cocultured on TNX-null fibroblasts were rather reduced than those of B16 melanoma cells cocultured on wild-type. We concluded that the absence of TNX in the extracellular environment might play an important role in enhancement of the detachment of B16 melanoma cells.
- 公益社団法人日本薬学会の論文
- 2002-11-01
著者
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Matsumoto Ken-ichi
Department of Biosignaling and Radioisotope Experiment, Center for Integrated Research in Science, S
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Matsumoto Ken-ichi
Dep. Of Biosignaling And Radioisotope Experiment Center For Integrated Res. In Sci. Shimane Univ.
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Matsumoto Ken-ichiro
Departments Of Physical Chemistry Showa Pharmaceutical University
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ARIGA Hiroyoshi
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Matsumoto K
Graduate School Of Bioresource And Bioenvironmental Sciences Kyushu Univ.
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Matsumoto K
Department Of Bioscience And Biotechnology Division Of Bioresource And Bioenvironmental Sciences Fac
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MINAMITANI Takeharu
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Ariga Hiroyoshi
Department Of Molecular Biology Graduate School Of Pharmaceutical Sciences Hokkaido University
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MATSUMOTO Ken-ichi
Denartment of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Minamitani Takeharu
Department Of Molecular Biology Graduate School Of Pharmaceutical Sciences Hokkaido University
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Matsumoto Ken-ichi
Department Of Bioresource Science Faculty Of Agriculture Shimane University
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Ariga H
Graduate School Of Pharmaceutical Sciences Hokkaido University
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Ariga Hiroyoshi
Deparnment Of Molecular Biology Graduate School Of Pharmaceutical Sciences Hokkaido University
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