Transcriptome Reprogramming Of Cd11b(+) Bone Marrow Cells By Pancreatic Cancer Extracellular Vesicles
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY(2020)
摘要
Pancreatic cancers (PC) are highly metastatic with poor prognosis, mainly due to delayed detection. We previously showed that PC-derived extracellular vesicles (EVs) act on macrophages residing in the liver, eliciting extracellular matrix remodeling in this organ and marked hepatic accumulation of CD11b(+) bone marrow (BM) cells, which support PC liver metastasis. We here show that PC-EVs also bind to CD11b(+) BM cells and induce the expansion of this cell population. Transcriptomic characterization of these cells shows that PC-EVs upregulate IgG and IgA genes, which have been linked to the presence of monocytes/macrophages in tumor microenvironments. We also report here the transcriptional downregulation of genes linked to monocyte/macrophage activation, trafficking, and expression of inflammatory molecules. Together, these results show for the first time the existence of a PC-BM communication axis mediated by EVs with a potential role in PC tumor microenvironments.
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关键词
tumor microenvironment, extracellular vesicles, macrophages, monocytes, metastasis, pancreatic cancer, exosomes, cancer
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