Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
PLoS One. 2011;6(12):e28607. doi: 10.1371/journal.pone.0028607. Epub 2011 Dec 14.
TROP2, a cell surface protein structurally related to EpCAM, is expressed in various carcinomas, though its function remains largely unknown. We examined the expression of TROP2 and EpCAM in fetal mouse tissues, and found distinct patterns in the ureteric bud of the fetal kidney, which forms a tree-like structure. The tip cells in the ureteric bud proliferate to form branches, whereas the trunk cells differentiate to form a polarized ductal structure. EpCAM was expressed throughout the ureteric bud, whereas TROP2 expression was strongest at the trunk but diminished towards the tips, indicating the distinct cell populations in the ureteric bud. The cells highly expressing TROP2 (TROP2(high)) were negative for Ki67, a proliferating cell marker, and TROP2 and collagen-I were co-localized to the basal membrane of the trunk cells. TROP2(high) cells isolated from the fetal kidney failed to attach and spread on collagen-coated plates. Using MDCK cells, a well-established model for studying the branching morphogenesis of the ureteric bud, TROP2 was shown to inhibit cell spreading and motility on collagen-coated plates, and also branching in collagen-gel cultures, which mimic the ureteric bud's microenvironment. These results together suggest that TROP2 modulates the interaction between the cells and matrix and regulates the formation of the ureteric duct by suppressing branching from the trunk during kidney development.
TROP2 是一种细胞表面蛋白，与 EpCAM 在结构上具有相关性，在各种癌中表达，但功能尚不清楚。我们检测了 TROP2 和 EpCAM 在胎鼠组织中的表达，在形成树状结构的胎儿肾脏输尿管芽中发现了不同的模式。输尿管芽的顶端细胞增殖形成分支，而主干细胞分化形成极化的导管结构。EpCAM 在整个输尿管芽中表达，而 TROP2 的表达在主干最强，但向尖端逐渐减弱，表明输尿管芽中有不同的细胞群。高表达 TROP2（TROP2(high)）的细胞对增殖细胞标志物 Ki67 呈阴性，TROP2 和胶原-I 共定位到主干细胞的基底膜。从胎肾分离出的 TROP2(high)细胞无法在涂有胶原的平板上附着和扩散。使用 MDCK 细胞，这是研究输尿管芽分支形态发生的成熟模型，表明 TROP2 抑制细胞在涂有胶原的平板上的扩散和迁移，并抑制胶原凝胶培养物中的分支，这模拟了输尿管芽的微环境。这些结果共同表明，TROP2 通过抑制主干的分支来调节细胞与基质之间的相互作用，并调节肾脏发育过程中输尿管导管的形成。
