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
|
リソース情報 |
ヒト・動物細胞 |
A431(RCB0202) |