Tumor-derived interleukin-1α and leukemia inhibitory factor promote extramedullary hematopoiesis.

Autor: Barisas DAG; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.; Immunology Program, Washington University School of Medicine, St. Louis, Missouri, United States of America.; Medical Scientist Training Program, Washington University School of Medicine, St. Louis, Missouri, United States of America., Kabir AU; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America., Wu J; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America., Krchma K; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America., Kim M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America., Subramanian M; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America., Zinselmeyer BH; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America., Stewart CL; Developmental and Regenerative Biology, A*STAR Skin Research Laboratories, Singapore, Singapore., Choi K; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.; Immunology Program, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2023 May 03; Vol. 21 (5), pp. e3001746. Date of Electronic Publication: 2023 May 03 (Print Publication: 2023).
DOI: 10.1371/journal.pbio.3001746
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Barisas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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