Loberg Robert D, Day LaShon L, Dunn Rodney, Kalikin Linda M, Pienta Kenneth J
Department of Urology, University of Michigan Urology Center, Ann Arbor, MI, USA.
Neoplasia. 2006 Jan;8(1):69-78. doi: 10.1593/neo.05679.
Decay-accelerating factor (CD55) is a member of membrane-bound complement-regulatory proteins. CD55 expression correlates with poor survival in patients with colorectal cancer and has been implicated in the survival and tumorigenesis of blood-borne malignancies. Histologic analysis of clinical specimens from patients with advanced prostate cancer revealed an increase in CD55 expression in prostate tumor epithelial cells. CD55 was shown to be functionally active and to inhibit complement-mediated lysis in PC-3 and DU145 cells. The percentage of lysis was correlative with the CD55 expression profile observed in these prostate cancer cell lines. These data suggest that CD55 is an important regulator of prostate cancer cell survival. As a result, we have hypothesized that CD55 expression on prostate cancer cells promotes cell survival and contributes to the metastatic potential of prostate cancer cells. To determine the role of CD55 in prostate cancer tumorigenesis and metastasis, we generated PC-3(Luc) prostate cancer cells with CD55 siRNA-targeted disruption. We found that PC-3(Luc)/CD55 siRNA constructs in SCID mice resulted in a significant attenuation of overall tumor burden. Further investigation into the mechanisms of CD55-mediated tumor cell/microenvironment interaction is necessary to understand the role of CD55 in tumor cell survival and metastatic lesion formation.
衰变加速因子（CD55）是膜结合补体调节蛋白家族的一员。CD55的表达与结直肠癌患者的不良生存相关，并与血行性恶性肿瘤的生存和肿瘤发生有关。对晚期前列腺癌患者临床标本的组织学分析显示，前列腺肿瘤上皮细胞中CD55表达增加。研究表明，CD55具有功能活性，可抑制PC-3和DU145细胞中补体介导的细胞溶解。细胞溶解百分比与这些前列腺癌细胞系中观察到的CD55表达谱相关。这些数据表明，CD55是前列腺癌细胞生存的重要调节因子。因此，我们推测前列腺癌细胞上的CD55表达促进细胞存活，并有助于前列腺癌细胞的转移潜能。为了确定CD55在前列腺癌肿瘤发生和转移中的作用，我们构建了针对CD55的siRNA靶向破坏的PC-3（Luc）前列腺癌细胞。我们发现，在SCID小鼠中植入PC-3（Luc）/CD55 siRNA构建体可显著减轻总体肿瘤负担。进一步研究CD55介导的肿瘤细胞/微环境相互作用机制，对于理解CD55在肿瘤细胞存活和转移病灶形成中的作用至关重要。
