Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital- The Norwegian Radium Hospital, 0379 Oslo, Norway.
Mol Cell Proteomics. 2012 Jul;11(7):M111.012914. doi: 10.1074/mcp.M111.012914. Epub 2012 Mar 28.
Cancer biomarkers are invaluable tools for cancer detection, prognosis, and treatment. Recently, microvesicles have appeared as a novel source for cancer biomarkers. We present here the results from a proteomic analysis of microvesicles released to the extracellular environment by the metastatic prostate cancer cell line PC-3. Using nanocapillary liquid chromatography-tandem mass spectrometry 266 proteins were identified with two or more peptide sequences. Further analysis showed that 16% of the proteins were classified as extracellular and that intracellular proteins were annotated in a variety of locations. Concerning biological processes, the proteins found in PC-3 cell-released microvesicles are mainly involved in transport, cell organization and biogenesis, metabolic process, response to stimulus, and regulation of biological processes. Several of the proteins identified (tetraspanins, annexins, Rab proteins, integrins, heat shock proteins, cytoskeletal proteins, 14-3-3 proteins) have previously been found in microvesicles isolated from other sources. However, some of the proteins seem to be more specific to the vesicular population released by the metastatic prostate cancer PC-3 cell line. Among these proteins are the tetraspanin protein CD151 and the glycoprotein CUB domain-containing protein 1. Interestingly, our results show these proteins are promising biomarkers for prostate cancer and therefore candidates for clinical validation studies in biological fluids.
癌症生物标志物是癌症检测、预后和治疗的宝贵工具。最近，微泡作为癌症生物标志物的一种新来源出现了。我们在此介绍了对转移性前列腺癌细胞系 PC-3 释放到细胞外环境的微泡进行蛋白质组学分析的结果。使用纳毛细管液相色谱-串联质谱法，鉴定出了 266 种具有两个或更多肽序列的蛋白质。进一步分析表明，16%的蛋白质被分类为细胞外蛋白质，而细胞内蛋白质则在多种位置被注释。关于生物过程，在 PC-3 细胞释放的微泡中发现的蛋白质主要涉及运输、细胞组织和生物发生、代谢过程、对刺激的反应以及生物过程的调节。鉴定出的几种蛋白质（四跨膜蛋白、膜联蛋白、Rab 蛋白、整合素、热休克蛋白、细胞骨架蛋白、14-3-3 蛋白）以前在从其他来源分离的微泡中也有发现。然而，一些蛋白质似乎更特异于转移性前列腺癌 PC-3 细胞系释放的囊泡群体。这些蛋白质包括四跨膜蛋白 CD151 和糖蛋白 CUB 结构域包含蛋白 1。有趣的是，我们的结果表明这些蛋白质是前列腺癌有前途的生物标志物，因此是生物体液临床验证研究的候选者。
