Johns Hopkins Bayview Proteomics Center, Department of Medicine, Division of Cardiology, School of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA.
Proteomics. 2012 Feb;12(4-5):722-35. doi: 10.1002/pmic.201100346. Epub 2012 Jan 19.
The proteins secreted by various cells (the secretomes) are a potential rich source of biomarkers as they reflect various states of the cells at real time and at given conditions. To have accessible, sufficient and reliable protein markers is desirable as they mark various stages of disease development and their presence/absence can be used for diagnosis, prognosis, risk stratification and therapeutic monitoring. As direct analysis of blood/plasma, a common and noninvasive patient screening method, can be difficult for candidate protein biomarker identification, the alternative/complementary approaches are required, one of them is the analysis of secretomes in cell conditioned media in vitro. As the proteins secreted by cells as a response to various stimuli are most likely secreted into blood/plasma, the identification and pre-selection of candidate protein biomarkers from cell secretomes with subsequent validation of their presence at higher levels in serum/plasma is a promising approach. In this review, we discuss the proteins secreted by three progenitor cell types (smooth muscle, endothelial and cardiac progenitor cells) and two adult cell types (neonatal rat ventrical myocytes and smooth muscle cells) which can be relevant to cardiovascular research and which have been recently published in the literature. We found, at least for secretome studies included in this review, that secretomes of progenitor and adult cells overlap by 48% but the secretomes are very distinct among progenitor cell themselves as well as between adult cells. In addition, we compared secreted proteins to protein identifications listed in the Human Plasma PeptideAtlas and in two reports with cardiovascular-related proteins and we performed the extensive literature search to find if any of these secreted proteins were identified in a biomarker study. As expected, many proteins have been identified as biomarkers in cancer but 18 proteins (out of 62) have been tested as biomarkers in cardiovascular diseases as well.
各种细胞分泌的蛋白质(分泌组)是生物标志物的潜在丰富来源,因为它们反映了细胞在特定条件下的实时状态。拥有可及的、充足的和可靠的蛋白质标志物是理想的,因为它们标志着疾病发展的各个阶段,其存在/缺失可用于诊断、预后、风险分层和治疗监测。由于直接分析血液/血浆(一种常见的非侵入性患者筛选方法)对于候选蛋白生物标志物的鉴定可能较为困难,因此需要替代/补充方法,其中之一是在体外分析细胞条件培养基中的分泌组。由于细胞对各种刺激的反应所分泌的蛋白质最有可能分泌到血液/血浆中,因此从细胞分泌组中鉴定和预选候选蛋白生物标志物,并随后验证其在血清/血浆中的水平更高,是一种很有前途的方法。在这篇综述中,我们讨论了三种祖细胞类型(平滑肌、内皮和心脏祖细胞)和两种成体细胞类型(新生大鼠心室肌细胞和成体平滑肌细胞)分泌的蛋白质,这些蛋白质与心血管研究相关,并在最近的文献中有所报道。我们发现,至少对于包括在这篇综述中的分泌组研究,祖细胞和成体细胞的分泌组有 48%的重叠,但分泌组在祖细胞之间以及成体细胞之间也非常不同。此外,我们将分泌蛋白与人类血浆肽图谱以及两份与心血管相关蛋白的报告中列出的蛋白鉴定进行了比较,并进行了广泛的文献检索,以查找这些分泌蛋白中是否有任何一种在生物标志物研究中被鉴定出来。不出所料,许多蛋白质已被鉴定为癌症的生物标志物,但其中 18 种(62 种中的 18 种)也已被测试为心血管疾病的生物标志物。