Paracrine factor and cell-cell contact-mediated induction of protease and c-ets gene expression in malignant keratinocyte/dermal fibroblast cocultures.

Paracrine factor and cell-cell contact-mediated induction of protease and c-ets gene expression in malignant keratinocyte/dermal fibroblast cocultures.
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恶性角质形成细胞/真皮成纤维细胞共培养物中旁分泌因子和细胞-细胞接触介导的蛋白酶和 c-ets 基因表达的诱导。

DOI:
10.1006/excr.1994.1183
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发表时间:
1994
影响因子:
3.7
通讯作者:
Bowden,GT
Bowden,GT
中科院分区:
医学3区
文献类型:
--
作者:
Borchers,AH;Powell,MB;Fusenig,NE;Bowden,GT

文献摘要

被引文献

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这项研究的目的是描述导致皮肤鳞状细胞癌中蛋白水解酶基因表达诱导的间质-上皮相互作用。人鳞状细胞癌细胞系II4与原代人包皮成纤维细胞共培养,诱导尿激酶型纤溶酶原激活物(UPA)、基质溶酶、92 kDa IV型胶原酶以及丝氨酸和基质金属蛋白酶家族中几个基因的转录激活物c-Ets的mRNA表达。UPA和c-Ets的诱导定位于成纤维细胞群。UPA的诱导依赖于细胞与肿瘤细胞群体的接触,而c-Ets的诱导是细胞与细胞接触和肿瘤细胞衍生的可溶性因子共同作用的结果。相比之下,基质溶素的诱导定位于肿瘤细胞,Northern和Western分析表明,这种诱导发生在成纤维细胞衍生的可溶性因子的反应中。这些数据表明,旁分泌因子和间质成纤维细胞与上皮性肿瘤细胞之间的细胞-细胞接触都可以影响蛋白酶基因的表达。
The purpose of this study was to characterize stromal-epithelial interactions that result in induction of protease gene expression in squamous cell carcinoma of the skin. Coculture of the human squamous cell carcinoma cell line II4 with primary human foreskin fibroblasts was observed to induce mRNA expression of urokinase-type plasminogen activator (uPa), matrilysin, 92-kDa type IV collagenase, and c-ets, a transcriptional activator of several genes within the serine and matrix metalloprotease families. uPA and c-etsinduction were localized to the fibroblast cell population. uPa induction was found to be dependent upon cell-cell contact with the tumor cell population, whereas c-etsinduction was due to a combination of cell-cell contact and a tumor cell-derived soluble factor. In contrast, matrilysin induction localized to the tumor cells and was shown by Northern and Western analyses to occur in response to a fibroblast-derived soluble factor. These data demonstrate that both paracrine factors and cell-cell contact between stromal fibroblasts and epithelial tumor cells can influence protease gene expression.