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脂肪来源间充质干细胞分泌的外泌体通过增加COLGALT2表达促进骨肉瘤转移和增殖。

Exosomes Secreted by Adipose-Derived Mesenchymal Stem Cells Foster Metastasis and Osteosarcoma Proliferation by Increasing COLGALT2 Expression.

作者信息

Wang Yan, Chu Yijing, Li Kun, Zhang Guoqing, Guo Zhu, Wu Xiaolin, Qiu Chensheng, Li Yan, Wan Xin, Sui Jing, Zhang Dan, Xiang Hongfei, Chen Bohua

机构信息

Department of Spinal Surgery, Qingdao University Affiliated Hospital, Qingdao, China.

Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

Front Cell Dev Biol. 2020 May 25;8:353. doi: 10.3389/fcell.2020.00353. eCollection 2020.

DOI:10.3389/fcell.2020.00353
PMID:32523950
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7262406/
Abstract

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 . Conversely, COLGALT2 overexpression promoted U-2OS cell invasion, migration and proliferation . 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.

摘要

目的

人胶原蛋白β(1-O)半乳糖基转移酶2（COLGALT2）是胶原蛋白糖基化过程中的一种重要酶，但其在癌症中的生物学功能尚未完全明确。我们之前的研究表明，在骨肉瘤微环境中，脂肪来源的间充质干细胞（ADSCs）具有促进癌症的作用，但其确切机制仍不清楚。本研究的目的是探讨COLGALT2在ADSCs促进骨肉瘤作用中的作用。

材料和方法

在本研究中，我们比较了原发性和转移性骨肉瘤组织中COLGALT2的表达，发现转移组织中COLGALT2水平显著更高。然后，我们分离并鉴定了ADSCs分泌的外泌体。此外，我们评估了ADSC外泌体和COLGALT2在ADSCs促进骨肉瘤作用中的作用。

结果

我们的结果表明，ADSC外泌体可以促进骨肉瘤细胞的侵袭、迁移和增殖，同时增加COLGALT2的表达。MG63细胞中COLGALT2的抑制抑制了ADSC外泌体介导的骨肉瘤细胞侵袭、迁移和增殖。相反，COLGALT2的过表达促进了U-2OS细胞的侵袭、迁移和增殖。此外，如在骨肉瘤裸鼠模型中所示，COLGALT2的抑制减弱了转移和肿瘤生长，而ADSC外泌体促进了肿瘤进展。

结论

根据这些数据，ADSC外泌体通过增加骨肉瘤细胞中COLGALT2的表达促进骨肉瘤进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/ecd45b307705/fcell-08-00353-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/53ebca470ccc/fcell-08-00353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/fcd3453e3c5b/fcell-08-00353-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/6b2198eaab0b/fcell-08-00353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/a333e6be6004/fcell-08-00353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/e8dea7c31f7d/fcell-08-00353-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/955735a23112/fcell-08-00353-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/d0ba01ecf778/fcell-08-00353-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/ecd45b307705/fcell-08-00353-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/53ebca470ccc/fcell-08-00353-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/fcd3453e3c5b/fcell-08-00353-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/6b2198eaab0b/fcell-08-00353-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/a333e6be6004/fcell-08-00353-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/e8dea7c31f7d/fcell-08-00353-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/955735a23112/fcell-08-00353-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/d0ba01ecf778/fcell-08-00353-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b7/7262406/ecd45b307705/fcell-08-00353-g008.jpg

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