National Key Laboratory of Medical Molecular Biology & Department of ImmunologyInstitute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
Department of Blood TransfusionTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Endocr Relat Cancer. 2018 Oct;25(10):879-891. doi: 10.1530/ERC-17-0547. Epub 2018 Jun 12.
Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) is related to increased risk of recurrence and poor prognosis. Tumour exosomes have been shown to be associated with metastasis of cancer cells. Therefore, we aim to identify the characteristics and biological functions of serum exosomes in lymph node metastases of PTC. We compared proteome profiles of serum-purified exosomes (SPEs) from PTC patients with LNM, PTC patients without LNM, and healthy donors, using a combination of liquid chromatography-tandem mass spectroscopy analyses and tandem mass tag label quantitation analysis. We identified 1569 proteins by two or more unique peptides. Compared with the SPEs of PTC patients without LNM, we found 697 differentially expressed proteins in the SPEs of PTC patients with LNM. Our results revealed overexpression of specific proteins with well-established links to cancer cell metastasis, such as SRC, TLN1, ITGB2 and CAPNS1. Consistent with mass spectrum results, we performed Western blot to detect the expression of these proteins in individual sample. Biological pathway analyses showed that integrin signalling was aberrantly activated in the SPEs of PTC patients with LNM compared to those without LNM. Our study reveals that SPEs of PTC patients with lymph node metastases promote BHT101 thyroid cancer cell invasiveness, but have no apparent influence on cell migration. In the serum exosomes of PTC patients with LNM, integrin-associated proteins are obviously upregulated. These proteomic findings will contribute to elucidation of the pathophysiological functions of tumour-derived exosomes.
甲状腺乳头状癌（PTC）的淋巴结转移（LNM）与复发风险增加和预后不良有关。肿瘤外泌体与癌细胞转移有关。因此，我们旨在确定 PTC 淋巴结转移患者血清外泌体的特征和生物学功能。我们使用液相色谱-串联质谱分析和串联质量标签标记定量分析相结合的方法，比较了有 LNM 的 PTC 患者、无 LNM 的 PTC 患者和健康供体的血清纯化外泌体（SPE）的蛋白质组谱。我们通过两个或更多独特肽鉴定了 1569 种蛋白质。与无 LNM 的 PTC 患者的 SPE 相比，我们在有 LNM 的 PTC 患者的 SPE 中发现了 697 种差异表达的蛋白质。我们的结果显示，与癌症细胞转移有明确联系的特定蛋白质表达上调，如 SRC、TLN1、ITGB2 和 CAPNS1。与质谱结果一致，我们进行了 Western blot 检测以检测这些蛋白质在个别样本中的表达。生物途径分析显示，与无 LNM 的患者相比，有 LNM 的患者的 SPE 中整合素信号通路异常激活。我们的研究表明，有 LNM 的 PTC 患者的 SPE 促进 BHT101 甲状腺癌细胞侵袭性，但对细胞迁移没有明显影响。在有 LNM 的 PTC 患者的血清外泌体中，整合素相关蛋白明显上调。这些蛋白质组学发现将有助于阐明肿瘤源性外泌体的病理生理功能。
