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, eliciting extracellular matrix remodeling in this organ and marked hepatic accumulation of C...

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Detalhes bibliográficos
Autor principal: Maia, J (author)
Outros Autores: Otake, AH (author), Poças, J (author), Carvalho, AS (author), Beck, HC (author), Magalhães, A (author), Matthiesen, R (author), Strano Moraes, MC (author), Costa-Silva, B (author)
Formato: article
Idioma:eng
Publicado em: 2020
Assuntos:
Texto completo:https://hdl.handle.net/10216/145270
País:Portugal
Oai:oai:repositorio-aberto.up.pt:10216/145270
Descrição
Resumo: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.