Research Paper Volume 15, Issue 22 pp 13163—13175
Hypoxia-regulated exosomes mediate M2 macrophage polarization and promote metastasis in chondrosarcoma
- 1 Department of Research, Taiwan Blood Services Foundation, Taipei, Taiwan
- 2 The Director’s Office, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- 3 Translational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- 4 Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
- 5 Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
- 6 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
- 7 Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
- 8 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
- 9 Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
Received: July 4, 2023 Accepted: October 17, 2023 Published: November 21, 2023
https://doi.org/10.18632/aging.205230How to Cite
Copyright: © 2023 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Chondrosarcoma is a primary malignant bone tumor. Traditional therapy is not very effective, and it is prone to metastasis in the late stage. The tumor microenvironment (TME) plays a key role in the progression and metastasis of chondrosarcoma, and hypoxia is one of the key factors in the formation of TME. However, the detailed mechanism of how hypoxia affects tumor progression and metastasis in chondrosarcoma is still not fully understood. In this study, we focused on the mechanism of interaction between hypoxic chondrosarcoma cells (SW1353) and macrophages. Our results suggest that hypoxia enhances the release of exosomes from chondrosarcoma cells. These hypoxia-induced exosomes promoted macrophage polarization towards the M2 phenotype, characterized by the expression of CD163 and CD206, but not the M1 phenotype, characterized by CD86 expression. Further analysis revealed that M2 macrophages polarized by exosomes expressed arginase-1 and feedback to chondrosarcoma cells to promote migration. These results suggest that chondrosarcoma cells secrete more exosomes in a hypoxic microenvironment, and these hypoxia-derived exosomes induce the polarization of macrophages into an M2 phenotype, ultimately promoting the metastatic behavior of chondrosarcoma cells.
Abbreviations
ceRNA: competitive endogenous RNA; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; HIFs: hypoxia-inducible factors; IL-4: interleukin-4; IL-10: interleukin-10; iNOS: inducible nitric oxide synthase; lncRNA RAMP2-AS1: long non-coding RNA called RAMP2-AS1; MIF: macrophage migration inhibitory factor; mRNAs: messenger RNAs; NTA: nanoparticle tracking analysis; OS: osteosarcoma; PD-L1: programmed death-ligand 1; PMA: phorbol 12-myristate 13-acetate; PVDF: polyvinylidene fluoride; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; S.D.: standard deviation; TAMs: tumor-associated macrophages; TBST: Tris-Buffered Saline-Tween; TME: the tumor microenvironment; VEGF: vascular endothelial growth factor; VEGFR-2: vascular endothelial growth factor receptor 2; ZO-1: zonula occluden-1.