Transcriptome reprogramming of CD11b+ bone marrow cells by pancreatic cancer extracellular vesicles

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, preparing pre-metastatic niches that support metastasis to this organ. This process involves the binding of PC-EVs to Kupffer cells, followed by TGFß secretion and upregulation of fibronectin production by hepatic stellate cells, which supports hepatic accumulation of CD11b+ bone marrow (BM) cells and PC liver metastasis. We here show that PC-EVs preferentially bind to CD11b+ BM cells and induce the expansion of this cell population. Transcriptomic characterization 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 transcription downregulation of genes linked to monocytes/macrophages activation, trafficking and expression of inflammatory molecules. Together, these results demonstrate the existence of a PC-BM communication axis mediated by EVs with a potential role in PC tumor microenvironments. Overall design: Expression profiles of cd11b+ cells from PC-Evs educated mice and naive mice.