Osteosarcoma Cells Derived Exosome Activate Inflammatory Signaling Pathways in Lung Fibroblast Cells
- VernacularTitle:骨肉瘤细胞外泌体激活肺组织成纤维细胞炎性信号通路
- Author:
Xian-biao XIE
1
,
2
;
Li-li WEN
3
;
Dong-ming LV
1
,
2
;
Hong-bo LI
1
,
2
;
Wei-hai LIU
1
,
2
;
Yu-tong ZOU
1
,
2
;
Hao YAO
1
,
2
;
Jing-nan SHEN
1
,
2
Author Information
1. Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510058, China
2. Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou 510058, China
3. Department of Anesthesiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
- Publication Type:Journal Article
- Keywords:
exosome;
osteosarcoma;
fibroblast cell;
inflammatory microenvironment
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2020;41(4):509-514
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To investigate the function and molecular mechanism of osteosarcoma cells derived exosome on microenvironment of target organs. 【Methods】 The osteosarcoma derived exosomes were extracted and injected into nude mice through tail vein after PKH26 fluorescence staining. The liver, spleen, lung, kidney and brain tissues were extracted 24 hours later and then the amount of red fluorescence in different fields was counted under fluorescence microscope. The uptake of exosomes in different types of cells was detected by immunofluorescence. 143B derived exosomes were co-cultured with human lung fibroblasts, and the uptake was detected by fluorescence microscopy. The expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α were detected by RT-qPCR, while the changes of p-p65 in inflammatory signaling pathway of NF- κB and p-ERK, p-p38 in MAPK signaling were detected by western blotting. 【Results】 TSG101, Flotillin-1, CD63 and CD9 were expressed in 143B derived exosomes, and Calnexin expression was absent(P<0.05). The exosomes presented a saucer-like structure under electron microscope. The size of the exosomes is(141.92± 52.85) nm. The exosomes distributed more in lung tissue than liver, kidney, spleen and brain after injection through the tail vein of nude mice(P<0.05). The mRNA levels of inflammatory cytokines IL-1β, IL-6and TNF-α were significantly increased in human lung fibroblast cells after incubation with 143B exosomes(P<0.05). p-p65, p-ERK and p-p38MAPK were significantly up-regulated(P<0.05) . 【Conclusions】 Osteosarcoma cells derived exosomes could activate inflammatory signaling pathway NF-κB and MAPK, and up-regulate the expression of the inflammatory cytokines IL-1β, IL-6 and TNF-α in lung fibroblast cells.
