Tumor-derived Interleukin-1α and Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis

Overview

Journal PLoS Biol

Specialty Biology

Date 2023 May 3

PMID 37134077

Authors

Derek A G Barisas

Ashraf Ul Kabir

Jun Wu

Karen Krchma

Minseo Kim

Madhav Subramanian

Bernd H Zinselmeyer

Colin L Stewart

Kyunghee Choi

Affiliations

Soon will be listed here.

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.

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