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

Authors and affiliations:
Joana Maia^1,2, Andreia Hanada Otake^1,3, Juliana Poças^4,5,6, Ana Sofia Carvalho⁷, Hans Christian Beck⁸, Ana Magalhães^4,5, 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

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.

Journal: Frontiers in Cell Developmental Biology

Link: https://www.frontiersin.org/articles/10.3389/fcell.2020.592518/full