Kleinerman D I, Dinney C P, Zhang W W, Lin S H, Van N T, Hsieh J T
Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1996 Aug 1;56(15):3431-5.
Recently, we demonstrated that an immunoglobulin-like cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer. It is known that C-CAM is expressed in many epithelial cell types. In this study, we tested the possibility that C-CAM may also suppress bladder cancer progression. We used an orthotopic tumor model, which provides a relevant organ condition for examining the interaction between primary tumor cells and their microenvironment; this interaction has a critical impact on the behavior of carcinoma. We constructed a recombinant adenovirus expressing C-CAM1 (an isoform of C-CAM) and infected the 253J B-V cell line, a tumorigenic human bladder carcinoma subline. In vitro, C-CAM1 protein was detected in C-CAM1 adenovirus-infected cells but not in antisense control virus-infected cells, and the levels of expression showed dose dependency. When these cells were injected orthotopically in nude mice, we found that the increased expression of C-CAM1 in the 253J B-V cells repressed the growth of 253J B-V-induced tumors. Taken together, these data indicate that C-CAM1 is a potent tumor suppressor in human bladder cancer.
最近，我们证明了一种免疫球蛋白样细胞粘附分子C-CAM在前列腺癌中作为一种肿瘤抑制因子发挥作用。已知C-CAM在多种上皮细胞类型中表达。在本研究中，我们测试了C-CAM也可能抑制膀胱癌进展的可能性。我们使用了原位肿瘤模型，该模型为研究原发性肿瘤细胞与其微环境之间的相互作用提供了相关的器官条件；这种相互作用对癌的行为有至关重要的影响。我们构建了一种表达C-CAM1（C-CAM的一种同工型）的重组腺病毒，并感染了253J B-V细胞系，这是一种致瘤性人膀胱癌细胞亚系。在体外，在感染C-CAM1腺病毒的细胞中检测到了C-CAM1蛋白，而在感染反义对照病毒的细胞中未检测到，并且表达水平呈剂量依赖性。当将这些细胞原位注射到裸鼠体内时，我们发现253J B-V细胞中C-CAM1表达的增加抑制了253J B-V诱导的肿瘤的生长。综上所述，这些数据表明C-CAM1在人膀胱癌中是一种有效的肿瘤抑制因子。
