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Adhesive defect in extracellular matrix tenascin-X-null fibroblasts: a possible mechanism of tumor invasion.

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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)

Submitter: 有賀 寛芳

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