Abstract
Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, respectively. IL-1α induced TNFα expression in splenic HSPCs, which then activated splenic niche activity, while LIF induced proliferation of splenic niche cells. IL-1α and LIF display cooperative effects in activating EMH and are both up-regulated in some human cancers. Together, these data expand avenues for developing niche-directed therapies and further exploring EMH accompanying inflammatory pathologies like cancer.
Funder
National Institutes of Health
Foundation for Barnes-Jewish Hospital
Publisher
Public Library of Science (PLoS)
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience
Reference79 articles.
1. Homeostatic and pathogenic extramedullary hematopoiesis;CH Kim;J Blood Med,2010
2. Emerging principles in myelopoiesis at homeostasis and during infection and inflammation;JL Schultze;Immunity,2019
3. Contribution of extramedullary hematopoiesis to atherosclerosis. The spleen as a neglected hub of inflammatory cells;V Fernández-García;Front Immunol,2020
4. Extramedullary hematopoiesis in the absence of myeloproliferative neoplasm: Mayo Clinic case series of 309 patients;N Fan;Blood Cancer J,2018
5. Peripheral blood stem cell mobilization: the CXCR2 ligand GROβ rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties;LM Pelus;Exp Hematol,2006
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