Reference - Detail
| RRC ID | 39292 |
|---|---|
| Author | Sato T, Iwai M, Sakai T, Sato H, Seiki M, Mori Y, Ito A. |
| Title | 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. |
| Journal | 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. |
| Volume | 80(8) |
| Pages | 1137-43 |
| Published | 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 |
| Times Cited | 40 |
| WOS Category | ONCOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | A431(RCB0202) |