論文 - 詳細
| RRC ID | 39292 |
|---|---|
| 著者 | Sato T, Iwai M, Sakai T, Sato H, Seiki M, Mori Y, Ito A. |
| タイトル | Enhancement of membrane-type 1-matrix metalloproteinase (MT1-MMP) production and sequential activation of progelatinase A on human squamous carcinoma cells co-cultured with human dermal fibroblasts. |
| ジャーナル | Br J Cancer |
| Abstract |
Matrix metalloproteinase 2 (MMP-2)/gelatinase A plays an important role in tumour invasion and metastasis. Since MMP-2 is secreted as an inactive form (proMMP-2) from tumour and neighbouring stroma cells, the activation process is necessary to express the enzymic activity for degradation of extracellular matrix components. We herein reported that the activation of proMMP-2 was induced in human squamous carcinoma cells co-cultured with normal human dermal fibroblasts. When A431 cells were co-cultured with human fibroblasts at various cell ratios, 72-kDa proMMP-2 was converted to a 62-kDa active form through the appearance of a 64-kDa intermediate. The activation of proMMP-2 by co-culture was also observed in other carcinoma cell lines, HSC-4 and SAS, but not in normal human keratinocytes. We characterized by in vitro invasion assay that A431 cells in co-culture preferentially invaded through Matrigel and the increased invasive activity was inhibited by exogenously adding tissue inhibitor of metalloproteinases 2. The augmented proMMP-2 activation by co-culture was achieved by the increase in membrane type 1-MMP (MT1-MMP) production along with that of its mRNA level. The predominant appearance of MT1-MMP was immunologically observed in A431 cells, but not human fibroblasts of the co-culture. Furthermore, epidermal growth factor (EGF) enhanced the co-culture-mediated proMMP-2 activation by increasing the production and gene expression of MT1-MMP, and thereby tumour invasive activity was further augmented. These results suggest that the cell-cell contact between carcinoma cells and normal fibroblasts enhances the production of MT1-MMP followed by sequential activation of proMMP-2 on the tumour cell surface, which may be closely implicated in tumour invasion in vivo. |
| 巻・号 | 80(8) |
| ページ | 1137-43 |
| 公開日 | 1999-6-1 |
| DOI | 10.1038/sj.bjc.6690477 |
| PII | 6690477 |
| PMID | 10376963 |
| PMC | PMC2362364 |
| MeSH | Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / physiopathology* Cell Communication* Enzyme Precursors / biosynthesis Enzyme Precursors / metabolism* Fibroblasts / physiology* Gelatinases / biosynthesis Gelatinases / metabolism* Gene Expression Regulation, Neoplastic* Humans Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases / biosynthesis Metalloendopeptidases / metabolism* RNA, Messenger / biosynthesis Skin / cytology Tumor Cells, Cultured |
| IF | 5.791 |
| 引用数 | 40 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A431(RCB0202) |