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Adhesive defect in extracellular matrix tenascin-X-null fibroblasts: a possible mechanism of tumor invasion.
Title: | Adhesive defect in extracellular matrix tenascin-X-null fibroblasts: a possible mechanism of tumor invasion. |
Authors: | Minamitani, Takeharu Browse this author | Ariga, Hiroyoshi Browse this author →KAKEN DB | Matsumoto, Ken-Ichi Browse this author |
Keywords: | tenascin-X | matrix metalloproteinase | melanoma | extracellular matrix |
Issue Date: | Nov-2002 |
Publisher: | The Pharmaceutical Society of Japan |
Journal Title: | Biological & pharmaceutical bulletin |
Volume: | 25 |
Issue: | 11 |
Start Page: | 1472 |
End Page: | 1475 |
Publisher DOI: | 10.1248/bpb.25.1472 |
PMID: | 12419962 |
Abstract: | 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. |
Type: | article |
URI: | http://hdl.handle.net/2115/53743 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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