Exosomal Secretion of Cytoplasmic Prostate Cancer Xenograft-derived Proteins
Exosomal Secretion of Cytoplasmic Prostate Cancer Xenograft-derived Proteins
复制标题
DOI：
10.1074/mcp.m800443-mcp200
复制
发表时间：
2009-06-01
影响因子：
7
通讯作者：
Jenster, Guido
中科院分区：
文献类型：
--
作者：
Jansen, Flip H.;Krijgsveld, Jeroen;Jenster, Guido
前列腺癌（PCa）的新标志物是必要的，因为目前建立的标志物，如前列腺特异性抗原缺乏诊断特异性和预后价值。来自移植有人前列腺癌异种移植物的小鼠的血清的蛋白质组学分析导致鉴定出44种肿瘤衍生蛋白。除分泌蛋白外，我们还鉴定了几种胞质蛋白，其中大多数是蛋白酶体的亚基。天然凝胶电泳和夹心ELISA表明，这些亚基存在于异种移植小鼠血清中的蛋白酶体复合物。我们假设蛋白酶体亚基和其他细胞质蛋白在异种移植小鼠血清中的存在可以通过癌细胞分泌小泡（所谓的外泌体）来解释。因此，对从PCa细胞系分离的外来体的蛋白质含量进行质谱和蛋白质印迹分析。这导致了主要的细胞质蛋白的鉴定，其中几个先前已被确定在异种移植小鼠的血清中，包括蛋白酶体亚基。分离的外来体还含有RNA，包括基因融合TMPRSS 2-ERG产物。这些观察结果表明，尽管它们的功能没有明确定义，但癌症来源的外泌体为鉴定PCa的新生物标志物提供了可能性。Molecular & Cellular Proteomics 8：1192-1205，2009.
Novel markers for prostate cancer (PCa) are needed because current established markers such as prostate-specific antigen lack diagnostic specificity and prognostic value. Proteomics analysis of serum from mice grafted with human PCa xenografts resulted in the identification of 44 tumor-derived proteins. Besides secreted proteins we identified several cytoplasmic proteins, among which were most subunits of the proteasome. Native gel electrophoresis and sandwich ELISA showed that these subunits are present as proteasome complexes in the serum from xenograft-bearing mice. We hypothesized that the presence of proteasome subunits and other cytoplasmic proteins in serum of xenografted mice could be explained by the secretion of small vesicles by cancer cells, so-called exosomes. Therefore, mass spectrometry and Western blotting analyses of the protein content of exosomes isolated from PCa cell lines was performed. This resulted in the identification of mainly cytoplasmic proteins of which several had previously been identified in the serum of xenografted mice, including proteasome subunits. The isolated exosomes also contained RNA, including the gene fusion TMPRSS2-ERG product. These observations suggest that although their function is not clearly defined cancer-derived exosomes offer possibilities for the identification of novel bio-markers for PCa. Molecular & Cellular Proteomics 8: 1192-1205, 2009.