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


ABSTRACT: 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.

SUBMITTER: Maia J 

PROVIDER: S-EPMC7729189 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Transcriptome Reprogramming of CD11b<sup>+</sup> Bone Marrow Cells by Pancreatic Cancer Extracellular Vesicles.

Maia Joana J   Otake Andreia Hanada AH   Poças Juliana J   Carvalho Ana Sofia AS   Beck Hans Christian HC   Magalhães Ana A   Matthiesen Rune R   Strano Moraes Maria Carolina MC   Costa-Silva Bruno B  

Frontiers in cell and developmental biology 20201127


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<sup>+</sup> bone marrow (BM) cells, which support PC liver metastasis. We here show that PC-EVs also bind to CD11b<sup>+</sup> BM cells and induce the expansion of this cell population. Transcrip  ...[more]

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