Bindels E M, Vermey M, Rebel J M, Zwarthoff E C, Van Der Kwast T H
Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
Exp Cell Res. 1997 Sep 15;235(2):395-402. doi: 10.1006/excr.1997.3705.
A major problem in the management of bladder cancer is the high risk for recurrence of bladder tumors after transurethral resection. This has generally been attributed to the attachment and subsequent expansion of exfoliated tumor cells to the traumatized bladder wall. An in vitro cocultivation model was used to study the implantation and growth of human tumor cells in traumatized murine urothelium. Furthermore, we investigated in a time-course experiment whether stimulation of the regenerative activity of the normal urothelium by a growth factor could affect implantation and subsequent growth of bladder tumor cells. After inoculation on injured confluent cultures of murine urothelium, human T24 and SD bladder carcinoma cells preferentially attached to the denuded areas. SD cells expanded into the normal urothelium as a sharply demarcated tumor, while T24 cells infiltrated as single cells. Treatment of the primary urothelium with epidermal growth factor (EGF) stimulated the proliferation of the primary urothelium and reduced the implantation and growth of T24 considerably. EGF reduced the implantation of the SD tumor cells but could not prevent the further expansion at the expense of surrounding normal urothelium. Since EGF had no effect on migration or proliferation of SD or T24 cells, its modulation of expansive growth is most probably due to an increase in the regeneration of normal urothelium. This study suggests that recurrence of transitional cell carcinomas might in some instances be inhibited by stimulation of the regeneration of traumatized urothelium. The reported in vitro cocultivation model may be useful for studying additional factors involved in intraepithelial expansion of carcinoma cells.
膀胱癌治疗中的一个主要问题是经尿道切除术后膀胱肿瘤复发风险高。这通常归因于脱落的肿瘤细胞附着于受创伤的膀胱壁并随后增殖。我们使用体外共培养模型研究人肿瘤细胞在受创伤的鼠膀胱上皮中的植入和生长。此外，我们在一项时间进程实验中研究了生长因子刺激正常膀胱上皮的再生活性是否会影响膀胱肿瘤细胞的植入和随后的生长。将人T24和SD膀胱癌细胞接种到受伤的汇合鼠膀胱上皮培养物上后，它们优先附着于裸露区域。SD细胞作为边界清晰的肿瘤扩展到正常膀胱上皮中，而T24细胞则以单细胞形式浸润。用表皮生长因子（EGF）处理原代膀胱上皮可刺激原代膀胱上皮的增殖，并显著减少T24细胞的植入和生长。EGF减少了SD肿瘤细胞的植入，但无法阻止其以周围正常膀胱上皮为代价的进一步扩展。由于EGF对SD或T24细胞的迁移或增殖没有影响，其对扩展性生长的调节很可能是由于正常膀胱上皮再生增加。本研究表明，在某些情况下，刺激受创伤膀胱上皮的再生可能会抑制移行细胞癌的复发。报道的体外共培养模型可能有助于研究参与癌细胞上皮内扩展的其他因素。
