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恶性与良性唾液腺肿瘤患者肿瘤微环境来源的间充质干细胞样细胞的蛋白质组学研究

英文原题:Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors.

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Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors.

PubMed 2022/04/27(内容时间) Cell J Q4 · IF 2(JCR 2025)

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研究概要

恶性与良性 SGT 可能表现出不同的组织蛋白模式,而这些模式很可能与代谢通路相关。

中文摘要

唾液腺肿瘤(SGT)具有某些侵袭性和独特的临床病理行为,可能与肿瘤微环境成分,尤其是间充质干细胞(MSC)相关蛋白有关。然而,MSC 相关蛋白在 SGT 肿瘤发生中的作用尚未充分了解。本研究旨在从恶性和良性肿瘤组织中分离并表征 MSC,并鉴定两类 MSC 之间差异表达的蛋白质。

本实验研究从良性肿瘤(多形性腺瘤,n=5)和恶性肿瘤(黏液表皮样癌,n=5)组织中分离 MSC 样细胞,采用荧光标记抗体和流式细胞分析进行验证。通过双向聚丙烯酰胺凝胶电泳(2DE)和质谱鉴定差异表达蛋白。

分离细胞强表达 CD44、CD73、CD90、CD105 和 CD166 等 MSC 特征标志物,但不表达或仅弱表达 CD14、CD34 和 CD45。两类分离细胞均未表达或几乎不表达 CD24 和 CD133。此外,恶性组织分离的 MSC 中 Annexin A4(Anxa4)、延伸因子 1-δ(EF1-D)、FK506 结合蛋白 9(FKBP9)、胞质血小板活化因子乙酰水解酶 IB 亚基 β(PAFAH1B)、II 型转谷氨酰胺酶(TG2)和 S-甲酰谷胱甘肽水解酶(FGH)过表达。良性组织来源的 MSC 中则发现热休克蛋白 70(Hsp70)和角蛋白 II 型细胞骨架 7(CK-7)过表达。

良性和恶性 SGT 可能具有不同的组织蛋白表达模式,且这些差异很可能与代谢通路有关。但仍需在更多患者中开展研究,以确定这些蛋白作为癌症治疗新靶点的适用性。

展开英文摘要原文

Salivary gland tumors (SGTs) show some aggressive and peculiar clinicopathological behaviors that might be related to the components of the tumor microenvironment, especially mesenchymal stem cells (MSCs)-associated proteins. However, the role of MSCs-related proteins in SGTs tumorigenesis is poorly understood. This study aimed to isolate and characterize MSCs from malignant and benign tumor tissues and to identify differentially expressed proteins between these two types of MSCs.

In this experimental study, MSC-like cells derived from benign (pleomorphic adenoma, n=5) and malignant (mucoepidermoid carcinoma, n=5) tumor tissues were verified by fluorochrome antibodies and flow cytometric analysis. Differentially expressed proteins were identified using two-dimensional polyacrylamide gel electrophoresis (2DE) and Mass spectrometry.

Results showed that isolated cells strongly expressed characteristic MSCs markers such as CD44, CD73, CD90, CD105, and CD166, but they did not express or weakly expressed CD14, CD34, CD45 markers. Furthermore, the expression of CD24 and CD133 was absent or near absent in both isolated cells. Results also discovered overexpression of Annexin A4 (Anxa4), elongation factor 1-delta (EF1-D), FK506 binding protein 9 (FKBP9), cytosolic platelet-activating factor acetylhydrolase type IB subunit beta (PAFAH1B), type II transglutaminase (TG2), and s-formylglutathione hydrolase (FGH) in MSCs isolated from the malignant tissues. Additionally, heat shock protein 70 (Hsp70), as well as keratin, type II cytoskeletal 7 (CK-7), were found to be overexpressed in MSCs derived from the benign ones.

Malignant and benign SGTs probably exhibit a distinct pattern of tissue proteins that are most likely related to the metabolic pathway. However, further studies in a large number of patients are required to determine the applicability of identified proteins as new targets for cancer therapy.

论文信息

作者
Haghshenas MR、Erfani N、Khansalar S、Khademi B、Ashraf MJ、Razmkhah M、Ghaderi A
第一作者单位
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.Iran
通讯作者单位
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Email: ghaderia@sums.ac.ir.Iran
期刊
Cell journal2022 Apr
原文标识
PubMed 35674025 · DOI 10.22074/cellj.2022.7844