| Objective: Pancreatic cancer(PC)is one of the most lethal cancers with a high disease burden and its systemic and surgical treatments are associated with high complication rates.Now,it is an aggressive malignancy with a 5-year survival rate of around 8%and is the fourth leading cause of cancer-related deaths all over the world.Exosome plays a pivotal role in modulation of crosstalk between cancer cells and adipocytes in pancreatic cancer,but the molecular mechanisms need to further investigated.Methods: Exosomes isolated from supernatants of PC cells were characterized through Electron microscopy,Nanoparticle tracking analysis(NTA)and RNase A.In vitro co-culture system of adipocytes 3T3-L1 and PC cells was established.Functional assays,including EdU assay,qPCR,western blot,migration and invasion of Transwell assays,wound healing assays,real time cell analysis(RTCA)and tumor growth in vivo were performed to investigate exosome-transmitted linc-ROR in regulation of dedifferentiation of adipocytes,epithelial-mesenchymal transition(EMT)process.Results: We found that tumor-secreted linc-ROR could be incorporated into exosomes,transmitted to adipocytes in co-culture system,and upregulate HIF-1α/ZEB1 expression,which promote adipocytes dedifferentiating to fibroblast.can further promote expression of HIF-1α and ZEB1 in PC cells,induce EMT process.Conclusion: Based on the literature review and our study,tumor-secreted linc-ROR could be incorporated into exosomes and transmitted to adipocytes,they can activate the HIF-1α pathway,promote adipocytes to further promote expreesion of HIF-1α and linc-ROR in PC cells,induce the EMT,form a positive feedback loop between PC and adipocytes 3T3-L1,and finally enhance the proliferation,invasion and metastasis of PC.Our study provide the new insights for understanding mechanism of PC metastasis and also lead to identify a new molecular target for early detection and targeted therapy in patients with PC. |
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