CD10（中性内肽酶）缺失是人类前列腺癌中常见的早期事件。

Loss of CD10 (neutral endopeptidase) is a frequent and early event in human prostate cancer.

作者信息

Freedland Stephen J, Seligson David B, Liu Alvin Y, Pantuck Allan J, Paik Sun H, Horvath Steve, Wieder Jeffrey A, Zisman Amnon, Nguyen David, Tso Cho-Lea, Palotie Aarno V, Belldegrun Arie S

机构信息

Department of Urology, UCLA School of Medicine, Los Angeles, CA 90095-1738, USA.

出版信息

Prostate. 2003 Apr 1;55(1):71-80. doi: 10.1002/pros.10202.

DOI:10.1002/pros.10202

PMID:12640663

Abstract

BACKGROUND

We hypothesized that the aggressive LNCaP-derived androgen-independent cell line, CL1, might differ from LNCaP in their repertoire of cell surface markers and that these differences might typify changes that occur during clinical prostate cancer progression.

METHODS

The cell surface marker expression profiles of CL1 and LNCaP were examined using flow cytometry. Markedly differential gene expression was confirmed using RT-PCR and further examined using immunohistochemistry among the prostate cancer cell lines LAPC-4, LNCaP, CL1, CL2, DU145, and PC-3. The expression of the most markedly differentially expressed surface marker, CD10, was further explored in a tissue microarray containing radical prostatectomy samples from 219 hormone naïve prostate cancer patients.

RESULTS

There were marked differences in the expression of CD10, CD13, CD26, CD33, CD44, CD54, CD55, and CD104 between CL1 and LNCaP. Results from both the RT-PCR and immunohistochemistry confirmed the differential expression and found that CD10 demonstrated a pattern of expression in hormone sensitive but not hormone refractory cell lines. When CD10 expression was examined in a tissue microarray, CD10 expression was below the 25th percentile of matched normal prostate tissue in 68% of prostate cancers, below the median expression of matched normal prostate tissue in 86% of cancers, and completely absent in 34% of cancers. Samples of prostatic intraepithelial neoplasia demonstrated CD10 expression that was intermediate between normal prostatic tissue and prostate cancer. Among prostate cancer patients, CD10 expression did not correlate with Gleason score, pathological stage, or biochemical recurrence following radical prostatectomy.

CONCLUSIONS

These findings demonstrate that loss or decreased expression of CD10 is an early and frequent event in human prostate cancer and implicates CD10 as a potential therapeutic target for early stage hormone sensitive prostate cancer.

摘要

背景

我们推测源自LNCaP的侵袭性雄激素非依赖细胞系CL1在细胞表面标志物库方面可能与LNCaP不同，且这些差异可能代表临床前列腺癌进展过程中发生的变化。

方法

使用流式细胞术检测CL1和LNCaP的细胞表面标志物表达谱。通过逆转录聚合酶链反应（RT-PCR）确认明显的差异基因表达，并在前列腺癌细胞系LAPC-4、LNCaP、CL1、CL2、DU145和PC-3中进一步使用免疫组织化学进行检测。在包含219例未经激素治疗的前列腺癌患者根治性前列腺切除术样本的组织芯片中，进一步探究差异表达最明显的表面标志物CD10的表达情况。

结果

CL1和LNCaP之间在CD10、CD13、CD26、CD33、CD44、CD54、CD55和CD104的表达上存在显著差异。RT-PCR和免疫组织化学结果均证实了差异表达，并发现CD10在激素敏感而非激素难治性细胞系中呈现出一种表达模式。当在组织芯片中检测CD10表达时，68%的前列腺癌中CD10表达低于匹配正常前列腺组织的第25百分位数，86%的癌症中低于匹配正常前列腺组织的中位数表达，34%的癌症中完全缺失。前列腺上皮内瘤变样本显示CD10表达介于正常前列腺组织和前列腺癌之间。在前列腺癌患者中，CD10表达与Gleason评分、病理分期或根治性前列腺切除术后的生化复发均无相关性。