PGRN-/- TAMs-derived exosomes inhibit breast cancer cell invasion and migration and its mechanism exploration.

Shujun Yue, Xiangsen Ye, Ting Zhou, Delu Gan, Husun Qian, Wenli Fang, Mengli Yao, Dian Zhang, He Shi, Tingmei Chen

Life sciences 2021 Jan 01

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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). To investigate the effects of exosomes derived from PGRN-/- TAMs on invasion and migration of breast cancer cells. 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. 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. Our study elucidates a new molecular mechanism of lung metastasis of breast cancer, so it may contribute to efficient prevention and therapeutic strategies. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Shujun Yue, Xiangsen Ye, Ting Zhou, Delu Gan, Husun Qian, Wenli Fang, Mengli Yao, Dian Zhang, He Shi, Tingmei Chen. PGRN-/- TAMs-derived exosomes inhibit breast cancer cell invasion and migration and its mechanism exploration. Life sciences. 2021 Jan 01;264:118687