Die Rolle von Zell-Zell- und Zell-Matrix-Interaktionen bei der Synthese und Aktivierung von MMP-2 und MMP-9 in epidermalen Tumorzellen in vitro und in vivo

细胞-细胞和细胞-基质相互作用在表皮肿瘤细胞体外和体内MMP-2和MMP-9合成和激活中的作用

• 批准号: 5250488
• 负责人: Privatdozentin Dr. Roswitha Nischt (†)
• 金额: --
• 依托单位: Klinik für Dermatologie und Venerologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2002-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5250488?language=en
• 关键词: Die; Rolle; von; Zell; und

The ability of tumor cells to invade surrounding tissue and to penetrate barriers such as basement membranes is one of the most important feature of the malignant phenotype. Studies performed over the last decade revealed that matrix metalloproteinases (MMPs) and in particular the gelatinases MMP-2 and MMP-9, which both are capable of degrading collagen type IV in basement membranes, play a crucial role during these processes. MMP gene expression is low or absent under normal conditions but is rapidly induced by altered cell-cell and cell-matrix interactions. However, the mechanisms underlying induction and activation of MMPs in tumor cells is not well understood. We plan to use an in vitro model system consisting of non-tumorigenic, epidermal HaCaT cells and HaCaT variants exhibiting different tumorigenic phenotypes, to analyse how basement membranes and their components regulate the expression and activation of these two MMPs and how tumor cell-host cell interactions influence these processes. Parallely, in vivo studies on human tumor speciments and experimental induced mouse tumors will be performed to verify the relevance of our in vitro data. This approach should be helpful to elucidate the mechanisms by which MMP-2 and MMP-9 might contribute to epidermal tumor progression.

肿瘤细胞侵入周围组织并穿透基底膜等屏障的能力是恶性表型最重要的特征之一。过去十年进行的研究表明，基质金属蛋白酶 (MMP)，特别是明胶酶 MMP-2 和 MMP-9，两者都能够降解基底膜中的 IV 型胶原蛋白，在这些过程中发挥着至关重要的作用。 MMP 基因表达在正常条件下较低或不存在，但通过改变的细胞-细胞和细胞-基质相互作用迅速诱导。然而，肿瘤细胞中 MMP 诱导和激活的机制尚不清楚。我们计划使用由非致瘤性表皮HaCaT细胞和表现出不同致瘤表型的HaCaT变体组成的体外模型系统，来分析基底膜及其成分如何调节这两种MMP的表达和激活以及肿瘤细胞-宿主细胞如何相互作用相互作用影响这些过程。同时，将对人类肿瘤样本和实验诱导的小鼠肿瘤进行体内研究，以验证我们体外数据的相关性。这种方法应该有助于阐明 MMP-2 和 MMP-9 可能促进表皮肿瘤进展的机制。