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比较蛋白质组学分析外泌体鉴定与乳腺癌转移相关的关键途径和蛋白标志物。

Comparative Proteomics Analysis of Exosomes Identifies Key Pathways and Protein Markers Related to Breast Cancer Metastasis.

机构信息

Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14214, USA.

New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY 14203, USA.

出版信息

Int J Mol Sci. 2023 Feb 17;24(4):4033. doi: 10.3390/ijms24044033.

DOI:10.3390/ijms24044033
PMID:36835443
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9967130/
Abstract

Proteomics analysis of circulating exosomes derived from cancer cells represents a promising approach to the elucidation of cell-cell communication and the discovery of putative biomarker candidates for cancer diagnosis and treatment. Nonetheless, the proteome of exosomes derived from cell lines with different metastatic capabilities still warrants further investigation. Here, we present a comprehensive quantitative proteomics investigation of exosomes isolated from immortalized mammary epithelial cells and matched tumor lines with different metastatic potentials in an attempt to discover exosome markers specific to breast cancer (BC) metastasis. A total of 2135 unique proteins were quantified with a high confidence level from 20 isolated exosome samples, including 94 of the TOP 100 exosome markers archived by ExoCarta. Moreover, 348 altered proteins were observed, among which several metastasis-specific markers, including cathepsin W (CATW), magnesium transporter MRS2 (MRS2), syntenin-2 (SDCB2), reticulon-4 (RTN), and UV excision repair protein RAD23 homolog (RAD23B), were also identified. Notably, the abundance of these metastasis-specific markers corresponds well with the overall survival of BC patients in clinical settings. Together, these data provide a valuable dataset for BC exosome proteomics investigation and prominently facilitate the elucidation of the molecular mechanisms underlying primary tumor development and progression.

摘要

从癌细胞来源的循环外泌体进行蛋白质组学分析代表了阐明细胞间通讯和发现用于癌症诊断和治疗的潜在生物标志物候选物的有前途的方法。尽管如此，不同转移能力的细胞系来源的外泌体的蛋白质组仍需要进一步研究。在这里，我们对来自具有不同转移潜能的永生化乳腺上皮细胞和匹配肿瘤系分离的外泌体进行了全面的定量蛋白质组学研究，试图发现与乳腺癌（BC）转移特异性的外泌体标志物。从 20 个分离的外泌体样本中定量了 2135 个具有高置信度的独特蛋白质，其中包括 ExoCarta 存档的前 100 个外泌体标志物中的 94 个。此外，观察到 348 个改变的蛋白质，其中包括几个转移特异性标志物，包括组织蛋白酶 W（CATW）、镁转运蛋白 MRS2（MRS2）、衔接蛋白-2（SDCB2）、网蛋白-4（RTN）和紫外线切除修复蛋白 RAD23 同源物（RAD23B）。值得注意的是，这些转移特异性标志物的丰度与 BC 患者在临床环境中的总体生存率很好地对应。这些数据共同为 BC 外泌体蛋白质组学研究提供了有价值的数据集，并显著促进了对原发性肿瘤发展和进展的分子机制的阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04f/9967130/d40562d0188e/ijms-24-04033-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04f/9967130/47322a9ddd9c/ijms-24-04033-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04f/9967130/adde4784e42e/ijms-24-04033-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04f/9967130/ab6e91163698/ijms-24-04033-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04f/9967130/d40562d0188e/ijms-24-04033-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04f/9967130/47322a9ddd9c/ijms-24-04033-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04f/9967130/adde4784e42e/ijms-24-04033-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04f/9967130/f4b7f7bb96a2/ijms-24-04033-g003.jpg
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