Mechanism of the regulation of prostate cancer stem cells by CAF:Based on the Wnt/β-catenin and SDF-1/CXCR4 pathways
10.13263/j.cnki.nja.2025.10.001
- VernacularTitle:从Wnt/β-catenin通路及SDF-1/CXCR4通路探讨癌相关成纤维细胞调控前列腺癌干细胞机制
- Author:
Haoran CHEN
1
;
Xudong ZHU
;
Jiazheng WANG
;
Yafei CHEN
;
Yilin WANG
;
Hao LIU
Author Information
1. 中国中医科学院广安门医院肿瘤科,北京 100053
- Publication Type:Journal Article
- Keywords:
prostate cancer;
cancer-associated fibroblast;
prostate cancer stem cells;
Wnt/β-catenin pathway;
SDF-1/CXCR4 pathway
- From:
National Journal of Andrology
2025;31(10):867-873
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which cancer-associated fibroblast(CAF)in the tumor microenvironment regulate key pathways in prostate cancer stem cells(PCSCs).Methods An in vitro co-culture system of CAF and PCSC was established to observe the effects of CAF on PCSC proliferation and sphere formation.Prostate cancer stem cells were treated with CAF conditioned medium pre-treated with Wnt inhibitor DKK-1 and SDF-1 neutralizing anti-body(MAB310).Western blot was used to detect the expression of β-catenin,CXCR4,CD133 and CD44 in PCSCs.And PCR was used to detect the expression of β-catenin,CXCR4,TCF,and LEF mRNA.TOPflash/FOPflash dual-luciferase reporter assays were conducted to detect the effects of SDF-1 on Wnt/β-catenin signaling activity in PCSCs.Results ELISA results showed that the secretion of Wnt3a and SDF-1 in CAF supernatant was significantly higher than that in WPMY-1 cells(P＜0.05).The A value of PCSCs co-cultured with CAF at a 1∶6 ratio was significantly higher than that of the PCSC-only group(P＜0.0 1),and CAF promoted sphere formation in PCSCs(P＜0.05).Western blot results showed that CAF-CM significantly increased the relative expression of β-catenin,CXCR4,CD133 and CD44 in PCSCs(P＜0.01).Compared to CAF-CM,CAFanti-Wnt-CM significantly reduced the expression of β-catenin,CD133 and CD44(P＜0.01).CAFanti-SDF-1-CM also significantly inhibited the expression of CXCR4,β-catenin,CD133 and CD44(P＜0.01).PCR results showed that CAFanti-SDF-1-CM inhibited the expression of β-catenin,CXCR4 and downstream Wnt signaling effectors TCF and LEF(P＜0.01).Dual-luciferase reporter assay results showed that luciferase activity in the CAFanti-SDF-1-CM group was significantly lower than that in the CAF-CM group(P＜0.05).Conclusion CAF reg-ulates the stemness of PCSCs through the Wnt/β-catenin and SDF-1/CXCR4 pathways.CXCR4 may enhance the mainte-nance of stemness by activating β-catenin.
