Growth factor-induced epidermal invasion of the dermis in human skin organ culture: dermal invasion correlated with epithelial cell motility.

Invasion & metastasis Pub Date : 1996-01-01
M E Zeigler, S Krause, S Karmiol, J Varani
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Abstract

We have developed a model of human squamous epithelial cell invasion in human skin organ culture. Epidermal invasion of the dermis occurs in this model when the tissue is exposed to an exogenous source of epithelial cell growth factor. In the present study we sought to determine to what extent growth factor-induced invasion correlates with the ability of the growth factor to induce epithelial cell motility. Histological examination of tissue treated with epidermal growth factor (EGF), hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1) or keratinocyte growth factor (KGF) showed that only HGF and EGF were inducers of invasion while KGF- and IGF-1-treated tissues were histologically similar to untreated controls. In parallel studies, HGF and EGF were found to be potent stimulators of epidermal keratinocyte motility while IGF-1 was less effective and KGF was even less so. None of the growth factors stimulated dermal fibroblast motility while HGF and to a lesser extent IGF-1 (but not EGF or KGF) stimulated motility of dermal vascular endothelial cells. Thus, there is a strong correlation between growth factor capacity to induce epidermal keratinocytes to invade the underlying dermal tissue and to induce motility in the invasive population of cells.

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人皮肤器官培养中生长因子诱导的真皮表皮侵袭:真皮侵袭与上皮细胞运动相关。
我们建立了人类鳞状上皮细胞在人体皮肤器官培养中的侵袭模型。在这个模型中,当组织暴露于外源性上皮细胞生长因子时,真皮的表皮入侵发生。在本研究中,我们试图确定生长因子诱导的侵袭在多大程度上与生长因子诱导上皮细胞运动的能力相关。对表皮生长因子(EGF)、肝细胞生长因子(HGF)、胰岛素样生长因子-1 (IGF-1)或角化细胞生长因子(KGF)处理的组织进行组织学检查显示,只有HGF和EGF是侵袭的诱导剂,而KGF和IGF-1处理的组织在组织学上与未处理的对照组相似。在平行研究中,HGF和EGF被发现是表皮角质形成细胞运动的有效刺激物,而IGF-1的效果较差,KGF的效果更差。没有生长因子刺激真皮成纤维细胞的运动,而HGF和IGF-1(但不是EGF或KGF)在较小程度上刺激真皮血管内皮细胞的运动。因此,生长因子诱导表皮角质形成细胞侵入下层真皮组织的能力与诱导侵入性细胞群的运动性之间存在很强的相关性。
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