Frontiers in Cell and Developmental Biology (Nov 2020)

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

  • Joana Maia,
  • Joana Maia,
  • Andreia Hanada Otake,
  • Andreia Hanada Otake,
  • Juliana Poças,
  • Juliana Poças,
  • Juliana Poças,
  • Ana Sofia Carvalho,
  • Hans Christian Beck,
  • Ana Magalhães,
  • Ana Magalhães,
  • Rune Matthiesen,
  • Maria Carolina Strano Moraes,
  • Bruno Costa-Silva

DOI
https://doi.org/10.3389/fcell.2020.592518
Journal volume & issue
Vol. 8

Abstract

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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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