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

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

doi:10.3389/fcell.2020.00353

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

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

Authors

Yan Wang¹, Yijing Chu², Kun Li³, Guoqing Zhang¹, Zhu Guo¹, Xiaolin Wu¹, Chensheng Qiu¹, Yan Li², Xin Wan², Jing Sui², Dan Zhang⁴, Hongfei Xiang¹, Bohua Chen¹

Affiliations

¹ Department of Spinal Surgery, Qingdao University Affiliated Hospital, Qingdao, China.
² Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, China.
³ Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
⁴ Department of Medicine, Qingdao University, Qingdao, China.

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 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.

Keywords: Homo sapiens collagen beta (1-O)galactosyltransferase 2; adipose-derived mesenchymal stem cells; exosomes; metastasis; osteosarcoma.