Identification of extracellular delta-catenin accumulation for prostate cancer detection.
Identification of extracellular delta-catenin accumulation for prostate cancer detection.
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DOI：
10.1002/pros.20902
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发表时间：
2009-03-01
期刊：
影响因子：
2.8
通讯作者：
Chen, Yan-Hua
中科院分区：
文献类型：
--
作者：
Lu, Qun;Zhang, Jiao;Allison, Ron;Gay, Hiram;Yang, Wan-Xi;Bhowmick, Neil A.;Frelix, Gloria;Shappell, Scott;Chen, Yan-Hua
前列腺癌是男性癌症死亡的第二大原因，早期发现对降低死亡率和提高生存率至关重要。δ-连环蛋白是一种独特的β-连环蛋白超家族蛋白，主要在脑中表达，但在人前列腺癌中上调。尽管它与疾病密切相关，但尚不清楚δ-连环蛋白是否在前列腺癌筛查中具有潜力，因为它是一种细胞内蛋白。在这项研究中，我们研究了前列腺癌患者尿液中δ-连环蛋白积聚的假设及其排泄到细胞外环境的潜在途径。对前列腺癌细胞培养物、人体组织活检和排泄尿液进行表征，以确定细胞外δ-连环蛋白积聚以及与外来体/前列腺体的共分离。我们在人前列腺癌组织的培养基和基质中鉴定了δ-连环蛋白。在培养的PC-3细胞中，δ-catenin与筏相关膜蛋白caveolin-1和糖基磷脂酰肌醇锚定蛋白CD 59部分共定位和共分离，表明其可能通过外泌体/前列腺酶体相关途径分泌到细胞外环境中。使用渥曼青霉素干扰内吞途径并不能阻断前列腺素体的排泄，但δ-连环蛋白过表达促进了小窝蛋白-1的细胞外积累。δ-连环蛋白、小窝蛋白-1和CD 59均在无细胞的人排泄尿前列腺体中检测到。前列腺癌患者尿中δ-Catenin免疫反应性显著增高（P<0.0005）。这项研究首次证明了尿液中δ-连环蛋白的细胞外积累，支持其用于非侵入性前列腺癌检测的潜在效用。
Prostate cancer is the second leading cause of cancer death in men, and early detection is essential to reduce mortality and increase survival. δ-Catenin is a unique β-catenin superfamily protein primarily expressed in the brain but is upregulated in human prostatic adenocarcinomas. Despite its close correlation with the disease, it is unclear whether δ-catenin presents the potential in prostate cancer screening because it is an intracellular protein. In this study, we investigated the hypothesis of δ-catenin accumulation in the urine of prostate cancer patients and its potential pathways of excretion into extracellular milieu. Prostate cancer cell cultures, human tissue biopsies, and voided urines were characterized to determine extracellular δ-catenin accumulation and co-isolation with exosomes/prostasomes. We identified δ-catenin in culture media and in the stroma of human prostate cancer tissues. In PC-3 cells in culture, δ-catenin was partially co-localized and co-isolated with raft-associated membrane protein caveolin-1 and glycosylphosphatidylinositol-anchored protein CD59, suggesting its potential excretion into extracellular milieu through exosome/prostasome associated pathways. Interference with endocytic pathway using wortmannin did not block prostasome excretion, but δ-catenin overexpression promoted the extracellular accumulation of caveolin-1. δ-Catenin, caveolin-1, and CD59 were all detected in cell-free human voided urine prostasomes. δ-Catenin immunoreactivity was significantly increased in the urine of prostate cancer patients (p<0.0005). This study demonstrated, for the first time, the extracellular accumulation of δ-catenin in urine supporting its potential utility for non-invasive prostate cancer detection.
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影响因子：
6.4
作者：
Burger, MJ;Tebay, MA;Gardiner, RA
通讯作者：
Gardiner, RA
影响因子：
3.5
作者：
Dhaese, S.;Jonckheere, V.;Van Troys, M.
通讯作者：
Van Troys, M.
影响因子：
3.3
作者：
Jones, SB;Lanford, GW;Lu, Q
通讯作者：
Lu, Q
DOI：
10.1016/j.bbrc.2008.02.069
发表时间：
2008-05-02
影响因子：
3.1
作者：
Kim, Kwonseop;Oh, Minsoo;Lu, Qun
通讯作者：
Lu, Qun
影响因子：
6.6
作者：
Stamey, TA;Johnstone, IM;Yemoto, CM
通讯作者：
Yemoto, CM