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

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.

• Authors: Takeharu Minamitani, Hiroyoshi Ariga, Ken-Ichi Matsumoto
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 25 Issue 11 Pg. 1472-5 (Nov 2002) ISSN: 0918-6158 [Print] Japan
• PMID: 12419962 (Publication Type: Journal Article)

Chemical References

• Tenascin
• tenascin X

Topics

• Animals
• Cell Adhesion (genetics)
• Coculture Techniques (methods)
• Extracellular Matrix (genetics, metabolism)
• Fibroblasts (metabolism)
• Melanoma, Experimental (genetics, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Inbred ICR
• Mice, Knockout
• Neoplasm Invasiveness (genetics, pathology)
• Tenascin (deficiency, genetics)
• Tumor Cells, Cultured