Extracellular vesicles secreted by adriamycin-resistant breast cancer cells promote the proliferation and migration of HUVEC and tumor angiogenesis
10.13602/j.cnki.jcls.2025.09.08
- VernacularTitle:阿霉素耐药的乳腺癌细胞外囊泡促进HUVEC增殖、迁移及肿瘤血管新生
- Author:
Ke XI
1
;
Xiaoyu DING
;
Cheng WANG
;
Junjun WANG
;
Chunni ZHANG
Author Information
1. 南京大学医学院附属金陵医院&东部战区总医院检验科,南京 210002
- Publication Type:Journal Article
- Keywords:
breast cancer;
adriamycin resistance;
extracellular vesicle;
tumor angiogenesis
- From:
Chinese Journal of Clinical Laboratory Science
2025;43(9):673-679
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the regulatory effects and molecular mechanisms of extracellular vesicles(EVs)secreted by adri-amycin(ADR)-resistant breast cancer cells on vascular endothelial cells related to tumor microenvironment.Methods The ADR-sen-sitive breast cancer cell line(MCF-7)and its ADR-resistant counterpart(MCF-7-ADR)were established in vitro.Then,the EVs were isolated from the supernatant of cell culture using a commercial kit.The fluorescence labeling and tracking technology using PKH67 was used to validate the internalization of EVs by human umbilical vein endothelial cell(HUVEC).The effects of EVs on the proliferation,migration,and angiogenesis of HUVEC were assessed by the colony formation,scratch wound healing,and tube formation assays,re-spectively.The expression level of CD31 protein was detected by Western blot,and the levels of vascular endothelial growth factor(VEGF)in cell supernatant were determined by ELISA.The microRNA(miRNA)sequencing technology was utilized to identify the differentially expressed miRNAs in EVs secreted by ADR-resistant cells.Results Compared with the ADR-sensitive strain,the EVs secreted by the ADR-resistant strain significantly enhanced the proliferation(colony number increased by 38.7%,P=0.011),migra-tion(scratch healing rate improved by 42.3%,P=0.004),and tube formation ability(tube formation rates increased by 1.8 times and 2.3 times at 4 h and 16 h,respectively,P=0.044 and 0.010)of HUVEC.Western blot analysis showed that the expression level of CD31 in the EVs secreted by the ADR-resistant strain increased by 1.85 times compared with the ADR-sensitive strain(P=0.039).The results of ELISA showed that the expression level of VEGF increased by 2.12 times(P=0.012).The miRNA sequencing identified a differentially expressed miRNA profile.Conclusion The ADR-resistant breast cancer cells significantly enhance the proliferation,migration,and angiogenesis of vascular endothelial cells by secreting EVs rich in specific miRNA,and its mechanism may be related to the up-regulation of CD31/VEGF protein levels mediated by EVs,suggesting that the drug-resistant cells reshaping the tumor vascular microenvironment through EVs may become a new therapeutic target of chemotherapy resistance in breast cancer.
