Rebel J M, Thijssen C D, Vermey M, Delouvée A, Zwarthoff E C, Van der Kwast T H
Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
Cancer Res. 1994 Oct 15;54(20):5488-92.
The high recurrence rate of human bladder cancer can be attributed to intraepithelial expansion of tumor cells or shedding and subsequent implantation of tumor cells elsewhere in the bladder. E-Cadherin is a calcium-dependent cell-cell adhesion molecule, and loss of E-cadherin by tumor cells is associated with increased tumor aggressiveness. Here we demonstrate that E-cadherin is also an important determinant of the mechanisms which are involved in the recurrence rate of bladder cancer. In a recently developed in vitro cocultivation model, we studied the effect of E-cadherin expression on the intraepithelial expansion pattern of six different human bladder carcinoma cell lines into primary murine urothelium. Bladder carcinoma cells lacking E-cadherin infiltrate into the primary urothelium as individual cells (pagetoid pattern). In contrast, a sharp demarcation is observed between E-cadherin-positive bladder cancer cells and the primary urothelium (carcinoma in situ pattern). With the same model, we demonstrate that only E-cadherin-positive bladder carcinoma cell lines could attach to and colonize the intact primary urothelium. We hypothesize that it is the latter process that plays an important role in the high recurrence rate that is observed in some of the patients.
人类膀胱癌的高复发率可归因于肿瘤细胞的上皮内扩展或肿瘤细胞的脱落及随后在膀胱其他部位的种植。E-钙黏蛋白是一种钙依赖性细胞间黏附分子，肿瘤细胞E-钙黏蛋白的缺失与肿瘤侵袭性增加有关。在此，我们证明E-钙黏蛋白也是参与膀胱癌复发率机制的一个重要决定因素。在最近建立的体外共培养模型中，我们研究了E-钙黏蛋白表达对六种不同人类膀胱癌细胞系向原代小鼠尿路上皮上皮内扩展模式的影响。缺乏E-钙黏蛋白的膀胱癌细胞以单个细胞形式浸润到原代尿路上皮中（派杰样模式）。相反，在E-钙黏蛋白阳性的膀胱癌细胞与原代尿路上皮之间观察到明显的界限（原位癌模式）。使用同一模型，我们证明只有E-钙黏蛋白阳性的膀胱癌细胞系能够附着并定植于完整的原代尿路上皮。我们推测，正是后一过程在一些患者中观察到的高复发率中起重要作用。
