Inhibition of decay-accelerating factor (CD55) attenuates prostate cancer growth and survival in vivo
Inhibition of decay-accelerating factor (CD55) attenuates prostate cancer growth and survival in vivo
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DOI：
10.1593/neo.05679
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Pienta, Kenneth J.
中科院分区：
文献类型：
--
作者：
Loberg, Robert D.;Day, LaShon L.;Pienta, Kenneth J.
衰变加速因子 (CD55) 是膜结合补体调节蛋白的成员。 CD55 表达与结直肠癌患者的较差生存率相关，并且与血源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。 CD55 具有功能活性，可抑制 PC-3 和 DU145 细胞中补体介导的裂解。裂解百分比与在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是前列腺癌细胞存活的重要调节因子。因此，我们假设前列腺癌细胞上的 CD55 表达可促进细胞存活并有助于前列腺癌细胞的转移潜力。为了确定 CD55 在前列腺癌肿瘤发生和转移中的作用，我们生成了具有 CD55 siRNA 靶向破坏的 PC-3(Luc) 前列腺癌细胞。我们发现 SCID 小鼠中的 PC-3(Luc)/CD55 siRNA 构建体导致总体肿瘤负荷显着减轻。有必要进一步研究 CD55 介导的肿瘤细胞/微环境相互作用的机制，以了解 CD55 在肿瘤细胞存活和转移病灶形成中的作用。
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.