Transcriptome Reprogramming of CD11b+ Bone Marrow Cells by Pancreatic Cancer Extracellular Vesicles

• Main Authors: Joana Maia, Andreia Hanada Otake, Juliana Poças, Ana Sofia Carvalho, Hans Christian Beck, Ana Magalhães, Rune Matthiesen, Maria Carolina Strano Moraes, Bruno Costa-Silva
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-11-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: tumor microenvironment; extracellular vesicles; macrophages; monocytes; metastasis; pancreatic cancer
• Online Access: https://www.frontiersin.org/articles/10.3389/fcell.2020.592518/full

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.