Abstract
ObjectivesHomosapien 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 MethodsIn 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.ResultsOur 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.ConclusionAccording to these data, ADSC exosomes foster osteosarcoma progression by increasing COLGALT2 expression in osteosarcoma cells.
Highlights
MATERIALS AND METHODSIn children and adolescents, osteosarcoma is the most common and devastating bone cancer
Our results showed that adipose-derived stem cells (ADSCs) exosomes could foster the invasion, migration, and proliferation of osteosarcoma cells, together with increasing COLGALT2 expression
Because the expression of COLGALT2 may be related to tumor metastasis, we examined COLGALT2 expression in patients with osteosarcoma
Summary
MATERIALS AND METHODSIn children and adolescents, osteosarcoma is the most common and devastating bone cancer. The ever-increasing evidence indicates a network between cancer cells and the tumor microenvironment that fuels disease progression and metastasis (Avril et al, 2016; Baumann and Hennet, 2016). Osteosarcoma recurrence has been revealed after the use of autologous fat grafts, and adipose-derived stem cells (ADSCs) are abundant in intermuscular tissue. The exact mechanisms underlying these effects remain poorly understood, much evidence clearly indicates that ADSCs in the microenvironment contribute to tumor progression. Exosomes derived from stromal cells are integral for formation of the tumor microenvironment and have been involved in all stages of cancer progression (Guiho et al, 2018). Understanding the effects of ADSC exosomes in the osteosarcoma microenvironment may allow ADSCs to serve as cancer prevention targets for cancer therapy
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