Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner
Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner
复制标题
DOI：
10.1593/neo.10216
复制
发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Rustgi, Anil K.
中科院分区：
文献类型：
--
作者：
Andl, Claudia D.;McCowan, Kelsey M.;Rustgi, Anil K.
食管癌通常表现出E-钙粘蛋白（Ecad）和转化生长因子β（TGF β）受体II（T β RII）的协同丢失，具有高死亡率。在三维器官型培养模型系统中，表达Ecad和T β RII（ECdnT）的显性阴性突变体的食管角质形成细胞侵入到包埋有成纤维细胞的底层基质中。我们还发现，组织蛋白酶B诱导是必要的成纤维细胞介导的入侵。此外，在该生理环境中，ECdnT细胞通过分泌TGF β 1激活成纤维细胞，TGF β 1又被组织蛋白酶B激活。这些结果表明，上皮区室和周围的微环境之间的相互作用是至关重要的细胞外基质的入侵。
Esophageal cancer, which frequently exhibits coordinated loss of E-cadherin (Ecad) and transforming growth factor beta (TGF beta) receptor II (T beta RII), has a high mortality rate. In a three-dimensional organotypic culture model system, esophageal keratinocytes expressing dominant-negative mutant versions of both Ecad and T beta RII (ECdnT) invade into the underlying matrix embedded with fibroblasts. We also find that cathepsin B induction is necessary for fibroblast-mediated invasion. Furthermore, the ECdnT cells in this physiological context activate fibroblasts through the secretion of TGF beta 1, which, in turn, is activated by cathepsin B. These results suggest that the interplay between the epithelial compartment and the surrounding microenvironment is crucial to invasion into the extracellular matrix.