Bone marrow mesenchymal stem cell-derived exosomes promote proliferation, invasion and migration of renal cancer cells by regulating cholestanol metabolism

Di-san junyi daxue xuebao

LIU Xueyang¹  ZHANG Yao¹  WANG Hexi¹  NIE Dongzi¹  LIU Ming¹ 

[1] Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China;

关键词: renal cell carcinoma;    bone marrow mesenchymal stem cells;    exosome;    cholesterol metabolism;    cell proliferation;    neoplasm invasiveness;    cell migration;   

DOI  :  10.16016/j.1000-5404.202104189

来源: DOAJ

【 摘 要 】

Objective To explore the effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on the proliferation, invasion and migration and lipid metabolism of renal cell carcinoma (RCC) cells, and investigate the possible mechanism. Methods Firstly, the exosomes derived from mouse BMSCs were identified by transmission electron microscopy and Western blotting. The exosomes uptake experiment of BMSCs was subsequently used to verify whether the derived exosomes could be absorbed by renal cancer cells. RCC Renca cells were divided into control (PBS) and experiment group (20 μg/mL derived exosomes). The proliferation, invasion and migration were measured by CCK-8 assay and Transwell assay, respectively. Metabolite levels were measured with liquid chromatography-mass spectrometry for the differences between the 2 groups of cells. Finally, Western blotting and real-time PCR (qRT-PCR) were utilized to detect the expression of key enzymes of cholesterol metabolism. Results Exosomes were successfully derived from the supernatant of mouse BMSCs. Transmission electron microscopy displayed that the mBMSC-derived exosomes showed typical cup-shaped vesicles. Western blotting showed that the levels of exosome-specific proteins CD63 and CD9 were highly expressed after exosome treatment. And the obtained exosomes could be uptaken by RCC cells. The derived exosome treatment significantly promoted proliferation (P < 0.05) and invasion and migration (P < 0.01) in RCC cells. Liquid chromatography-mass spectrometry indicated that the treatment also resulted in decreased level of tauroursodeoxycholic acid (TUDCA) (P < 0.05) and elevated level of cholesterol (P < 0.05) in RCC cells. Moreover, the treatment could affect the cholesterol metabolism of RCC cells via regulating the expression levels of HMGCR, CYP7A1 and CYP7B1, and thus promote the cell proliferation and invasion and migration. Conclusion BMSCs-derived exosomes can affect the cholesterol metabolism by regulating the key enzymes, and thus promote the proliferation, invasion and migration of RCC cells.

【 授权许可】

Unknown