Exosomes Secreted by Adipose-Derived Mesenchymal Stem Cells Foster Metastasis and Osteosarcoma Proliferation by Increasing COLGALT2 Expression
Exosomes Secreted by Adipose-Derived Mesenchymal Stem Cells Foster Metastasis and Osteosarcoma Proliferation by Increasing COLGALT2 Expression
复制标题
脂肪源性间充质干细胞分泌的外泌体通过增加 COLGALT2 表达促进转移和骨肉瘤增殖
DOI：
10.3389/fcell.2020.00353
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发表时间：
2020-05-25
影响因子：
5.5
通讯作者：
Chen, Bohua
中科院分区：
文献类型：
--
作者：
Wang, Yan;Chu, Yijing;Chen, Bohua
目的同型胶原β（1-O）半乳糖基转移酶2（COLGALT 2）是胶原糖基化过程中的重要酶，但其在肿瘤中的生物学功能尚不完全清楚。我们前期的研究表明，在骨肉瘤微环境中，脂肪间充质干细胞（ADSCs）表现出促癌作用，但确切机制尚不清楚。本研究的目的是探讨COLGALT 2在脂肪干细胞的骨肉瘤促进作用中的作用。材料与方法在这项研究中，我们比较了原发性和转移性骨肉瘤组织中COLGALT 2的表达，发现转移性组织表达的COLGALT 2水平显著较高。然后，我们分离并鉴定了ADSCs分泌的exosomes。此外，我们评估了ADSC外泌体和COLGALT 2在ADSC促进骨肉瘤作用中的作用。结果ADSC exosomes可促进骨肉瘤细胞的侵袭、迁移和增殖，并增加COLGALT 2的表达。抑制MG 63细胞中的COLGALT 2抑制ADSC外泌体介导的骨肉瘤细胞体外侵袭、迁移和增殖。相反，COLGALT 2过表达促进U-2 OS细胞的体外侵袭、迁移和增殖。此外，COLGALT 2抑制减弱了转移和肿瘤生长，ADSC外泌体促进了肿瘤进展，如在骨肉瘤的裸鼠模型中所证明的。结论ADSC外泌体通过增加骨肉瘤细胞中COLGALT 2的表达促进骨肉瘤的进展。
Objectives Homosapien collagen beta (1-O) galactosyl transferase 2 (COLGALT2) is an important enzyme during collagen glycosylation, yet its biological functions in cancer are incompletely understood. Our previous study revealed that in the osteosarcoma microenvironment, adipose-derived mesenchymal stem cells (ADSCs) demonstrate cancer-promoting effects, but the exact mechanisms remain unclear. The aim of this study was to investigate the role of COLGALT2 in the osteosarcoma-fostering effects of ADSCs. Materials and Methods In this study, we compared COLGALT2 expression between primary and metastatic osteosarcoma tissues and found that metastatic tissues expressed significantly higher COLGALT2 levels. Then, we isolated and identified exosomes secreted by ADSCs. Additionally, we assessed the roles of ADSC exosomes and COLGALT2 in the osteosarcoma-promoting effects of ADSCs. Results Our results showed that ADSC exosomes could foster the invasion, migration, and proliferation of osteosarcoma cells, together with increasing COLGALT2 expression. COLGALT2 inhibition in MG63 cells suppressed the ADSC exosome-mediated fostering of osteosarcoma cell invasion, migration and proliferation in vitro. Conversely, COLGALT2 overexpression promoted U-2OS cell invasion, migration and proliferation in vitro. Additionally, COLGALT2 inhibition attenuated metastasis and tumor growth, and ADSC exosomes promoted tumor progression, as demonstrated in a nude mouse model of osteosarcoma. Conclusion According to these data, ADSC exosomes foster osteosarcoma progression by increasing COLGALT2 expression in osteosarcoma cells.