2024-03-28T14:00:13Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/537432022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124Adhesive defect in extracellular matrix tenascin-X-null fibroblasts: a possible mechanism of tumor invasion.Minamitani, TakeharuAriga, HiroyoshiMatsumoto, Ken-Ichitenascin-Xmatrix metalloproteinasemelanomaextracellular matrix499AnimalsCell Adhesion/geneticsCoculture Techniques/methodsExtracellular Matrix/geneticsExtracellular Matrix/metabolismFibroblasts/metabolismMelanoma, Experimental/geneticsMelanoma, Experimental/metabolismMelanoma, Experimental/pathologyMiceMice, Inbred C57BLMice, Inbred CBAMice, Inbred ICRMice, KnockoutNeoplasm Invasiveness/geneticsNeoplasm Invasiveness/pathologyTenascin/deficiencyTenascin/geneticsTumor Cells, CulturedExtracellular 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.The Pharmaceutical Society of JapanJournal Articleapplication/pdfhttp://hdl.handle.net/2115/53743https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/53743/1/126_Ariga_2002_Biol_Pharm_Bull.pdf0918-6158Biological & pharmaceutical bulletin2511147214752002-11enginfo:pmid/12419962info:doi/10.1248/bpb.25.1472publisher