Unlabelled: Breast cancer is one of the most malignant diseases world-wide and ranks the first among female cancers. Progranulin (PGRN) plays a carcinogenic role in breast cancer, but its mechanisms are not clear. In addition, there are few reports on the relationship between PGRN and tumor-associated macrophages (TAMs).
Aims: To investigate the effects of exosomes derived from PGRN TAMs on invasion and migration of breast cancer cells.
Main Methods: Mouse breast cancer xenograft model was constructed to explore the effect of PGRN tumor environment (TME) on breast cancer. Flow cytometry was used to compare TAMs of wild type (WT) and PGRN tumor tissue. Transwell assay, wound healing assay and western blot were used to explore the effect of WT and PGRN TAMs and their exosomes on invasion, migration and epithelial-mesenchymal transition (EMT) of breast cancer cells. MicroRNA (miRNA) assay was used to find out the differentially expressed miRNA of negative control (NC) and siPGRN-TAMs exosomes. Quantitative PCR and luciferase report assay were used to explore the target gene.
Key Findings: The lung metastasis of breast cancer of PGRN mice was inhibited. PGRN TAMs inhibited invasion, migration and EMT of breast cancer cells through their exosomes. MiR-5100 of PGRN TAMs-derived exosomes was up-regulated, which might regulate expression of CXCL12, thereby inhibiting the CXCL12/CXCR4 axis, and ultimately inhibiting the invasion, migration and EMT of breast cancer cells.
Significance: Our study elucidates a new molecular mechanism of lung metastasis of breast cancer, so it may contribute to efficient prevention and therapeutic strategies.
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| http://dx.doi.org/10.1016/j.lfs.2020.118687 | DOI Listing |
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