Abstract
Fibroblasts play an important role in cancer development and progression. Small extracellular vesicles (sEVs) are one type of extracellular vesicles, which mediate the interaction between cancer-associated fibroblasts and cancer cells by transferring their contents. However, the roles of sEVs from cancer-associated fibroblasts on breast cancer stem cell properties are largely unraveled. The purpose of this study was to explore the roles of sEVs from cancer-associated fibroblasts on breast cancer progression. The miRNA array data showed a different miRNA profile between CAFs sEVs and normal fibroblasts sEVs. By verification using real-time RT-PCR, the data analysis indicated that miR-7641 levels were lower in sEVs from CAFs compared with NFs. The cellular functions were assayed and the results indicated that CAFs derived sEVs with low miR-7641 levels suppressed breast cancer cell survival, glycolysis, and stem cell properties via the HIF-1α pathway. Collectively, these findings indicated that sEVs from CAFs promoted breast cancer stem cell properties and glycolysis via miR-7641/HIF-1α, which was a possible new way for targeting breast cancer.
Highlights
Tumor stroma cells, cancer cells, extracellular matrix (ECM), and the secreted molecule or other contents constitute tumor microenvironment
The small extracellular vesicles (sEVs) from Carcinoma-associated fibroblasts (CAFs) increased breast cancer cell survival and metastasis ability To explore the role of CAFs sEVs on breast cancer cellular biological functions, firstly, sEVs from normal fibroblasts (NFs) and CAFs were isolated and taken by transmission electron microscopy (TEM) (Fig. 1A)
In order to learn whether CAFs sEVs have an influence on breast cancer cellular functions, SKBR3 and MDA-MB-231 cells were in the presence of CAFs-sEV or NFs-sEV
Summary
Cancer cells, extracellular matrix (ECM), and the secreted molecule or other contents constitute tumor microenvironment. Carcinoma-associated fibroblasts (CAFs) are the main cell type in tumor stroma and the emerging evidence indicates that CAFs play important roles in cancer progression [1, 2]. The cell-to-cell interaction between cancer cells and stromal cells is accomplished via paracrine mechanism including growth factors, chemokines, and proteases by extracellular vehicles (EVs) [6]. The sEVs from tumor stroma fibroblasts affect cancer cell biological functions and signal pathways [8]. MiR-522 from CAFs suppressed ferroptosis and promoted acquired drug resistance in gastric cancer [13]. CAFs exosomes suppress immune ability in breast Cancer by miR92/PD-L1 [14]. The functions and mechanism of sEVs from CAFs are still unclear
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