Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs.
10.3760/cma.j.cn112152-20200622-00586
- Author:
Yi Xuan DING
1
;
Yu Ting WANG
2
;
Wen Tong MEI
1
;
Zhi ZHENG
1
;
Yuan Xu QU
1
;
Kuo LIANG
1
;
Jia LI
1
;
Feng CAO
1
;
Fei LI
1
Author Information
1. Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
2. Capital Medical University, Clinical Medicine College, Beijing 100069, China.
- Publication Type:Journal Article
- Keywords:
Exosomes;
Human umbilical cord mesenchymal stromal cell;
MiRNAs;
Pancreatic neoplasms
- MeSH:
Mice;
Animals;
Humans;
MicroRNAs/metabolism*;
Exosomes/genetics*;
Sincalide/metabolism*;
Pancreatic Neoplasms/metabolism*;
Carcinoma, Pancreatic Ductal/genetics*;
Mesenchymal Stem Cells/metabolism*;
Umbilical Cord
- From:
Chinese Journal of Oncology
2023;45(1):50-55
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.
