微泡
生物
细胞培养中氨基酸的稳定同位素标记
癌症研究
癌基因
细胞生物学
肺癌
表皮生长因子受体
信号转导
细胞信号
自分泌信号
癌变
癌症
外体
蛋白质组学
细胞培养
细胞
细胞周期
小RNA
病理
医学
生物化学
基因
遗传学
作者
David Clark,William E. Fondrie,Austin J. Yang,Mao Li
标识
DOI:10.1016/j.jprot.2015.12.023
摘要
Exosomes are 30–100 nm sized membrane vesicles released by cells into the extracellular space that mediate intercellular communication via transfer of proteins and other biological molecules. To better understand the role of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules: Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). In total, we were able to quantify 721 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction, including EGFR, GRB2 and SRC, were enriched in NSCLC exosomes, and could actively regulate cell proliferation in recipient cells. This study's investigation of the NSCLC exosomal proteome has identified enriched protein cargo that can contribute to lung cancer progression, which may have potential clinical implications in biomarker development for patients with NSCLC. The high mortality associated with lung cancer is a result of late-stage diagnosis of the disease. Current screening techniques used for early detection of lung cancer lack the specificity for accurate diagnosis. Exosomes are nano-sized extracellular vesicles, and the increased abundance of select protein cargo in exosomes derived from cancer cells may be used for diagnostic purposes. In this paper, we applied quantitative proteomic analysis to elucidate abundance differences in exosomal protein cargo between two NSCLC cell lines with distinctive oncogene mutations and an immortalized normal bronchial epithelial cell line. This study revealed proteins associated with cell adhesion, the extracellular matrix, and a variety of signaling molecules were enriched in NSCLC exosomes. The present data reveals a protein profile associated with NSCLC exosomes that suggests a role these vesicles have in the progression of lung carcinogenesis, as well as identifies several promising candidates that could be utilized as a multi-marker protein panel in a diagnostic platform for NSCLC.
科研通智能强力驱动
Strongly Powered by AbleSci AI