Shotgun proteomics of thyroid carcinoma exosomes – Insight into the role of exosomal proteins in carcinogenesis and thyroid homeostasis

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects Pub Date : 2024-07-16 DOI:10.1016/j.bbagen.2024.130672

Magdalena Surman , Magdalena Wilczak , Urszula Jankowska , Bożena Skupień-Rabian , Małgorzata Przybyło

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引用次数: 0

Abstract

Background

Transport of molecules via exosomes is one of the factors involved in thyroid cancer development, and transported molecules may serve as cancer biomarkers. The aim of the study was to characterize protein content of thyroid-derived exosomes and their functional effect exerted on recipient cells.

Methods

LC-MS/MS proteomics of exosomes released by FTC and 8305C thyroid carcinoma cell lines, and Nthy-ori 3–1 normal thyroid follicular cells was performed, followed by bioinformatic analysis and functional tests (wound healing and Alamar Blue assays).

Results

Exosomes from Nthy-ori 3–1 cells had the highest number of 1504 proteins, while in exosomes from thyroid carcinoma FTC and 8305C cells 730 and 1304 proteins were identified, respectively. For proteins uniquely found in FTC- and 8305C-derived exosomes, enriched cancer-related gene ontology categories included cell adhesion, positive regulation of cell migration, N-glycosylation, drug resistance, and response to NK/T cell cytotoxicity. Furthermore, through label-free quantification (that identified differentially expressed proteins) and comparison with The Human Protein Atlas database several potential diagnostic and/or prognostic biomarkers were indicated. Finally, exosomes from FTC and 8305C cells displayed ability to stimulate migratory properties of recipient Nthy-ori 3–1 cells. Additionally, 8305C-derived exosomes increased recipient cell viability.

Conclusions

Multiple proteins identified in thyroid cancer-derived exosomes have a direct link to thyroid cancer progression. Also, in functional tests exosomes enhanced growth and dissemination of non-transformed thyroid cells.

General significance

The obtained results expands the knowledge concerning the role of exosomal proteins in thyroid cancer and indicate potential biomarkers for further evaluation in clinical settings.

Abstract Image

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甲状腺癌外泌体的散射蛋白质组学研究--洞察外泌体蛋白质在癌变和甲状腺稳态中的作用。

背景：通过外泌体转运分子是甲状腺癌发病的因素之一，转运的分子可作为癌症生物标志物。本研究旨在确定甲状腺外泌体的蛋白质含量及其对受体细胞的功能影响：方法：对FTC和8305C甲状腺癌细胞系以及Nthy-ori 3-1正常甲状腺滤泡细胞释放的外泌体进行LC-MS/MS蛋白质组学研究，然后进行生物信息分析和功能测试（伤口愈合和阿拉玛蓝试验）：结果：Nthy-ori 3-1细胞的外泌体中有最多的1504个蛋白质，而甲状腺癌FTC细胞和8305C细胞的外泌体中分别发现了730个和1304个蛋白质。在FTC和8305C细胞外泌体中唯一发现的蛋白质中，与癌症相关的基因本体类别包括细胞粘附、细胞迁移的正向调节、N-糖基化、耐药性和对NK/T细胞细胞毒性的反应。此外，通过无标记定量（确定不同表达的蛋白质）以及与人类蛋白质图谱数据库的比较，还发现了一些潜在的诊断和/或预后生物标志物。最后，来自 FTC 和 8305C 细胞的外泌体显示出刺激受体 Nthy-ori 3-1 细胞迁移的能力。此外，8305C衍生的外泌体提高了受体细胞的活力：结论：在甲状腺癌外泌体中发现的多种蛋白质与甲状腺癌的进展有直接联系。结论：在甲状腺癌外泌体中发现的多种蛋白质与甲状腺癌的进展有直接联系。此外，在功能测试中，外泌体还能促进非转化甲状腺细胞的生长和扩散：研究结果拓展了有关外泌体蛋白在甲状腺癌中作用的知识，并为临床进一步评估提供了潜在的生物标记物。

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来源期刊

Biochimica et biophysica acta. General subjects 生物-生化与分子生物学

CiteScore

6.40

自引率

0.00%

发文量

139

审稿时长

30 days

期刊介绍： BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.