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

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

Monday, 11.01.2021

Joana Maia1,2, Andreia Hanada Otake1,3, Juliana Poças4,5,6, Ana Sofia Carvalho7, Hans Christian Beck8, Ana Magalhães4,5, Rune Matthiesen7, Maria Carolina Strano Moraes1 and Bruno Costa-Silva1

1-Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal

2-Graduate Program in Areas of Basic and Applied Biology, University of Porto, Porto, Portugal

3-Center for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

4-i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

5-IPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal

6-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal

7-Computational and Experimental Biology Group, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade NOVA de Lisboa, Lisbon, Portugal

8-Centre for Clinical Proteomics, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark

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.

Frontiers in Cell Developmental Biology