TY - JOUR
T1 - Tumor-derived interleukin-1α and leukemia inhibitory factor promote extramedullary hematopoiesis
AU - Barisas, Derek A.G.
AU - Kabir, Ashraf Ul
AU - Wu, Jun
AU - Krchma, Karen
AU - Kim, Minseo
AU - Subramanian, Madhav
AU - Zinselmeyer, Bernd H.
AU - Stewart, Colin L.
AU - Choi, Kyunghee
N1 - Funding Information:
This work was supported by the NIH T32 AI007163 (to D.A.G.B), the NIH grants R37AI049653 (to B.H.Z.), R01HL149954 (to K.C.), R01HL55337(to K.C.), and by the Foundation for Barnes-Jewish Hospital, Grant Number: 5130 (Siteman Investment Program Research Development Awards to K.C.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Drs. M. Egeblad and David DeNardo for the gift of the MMTV-PyMT-B6 mice and PyMT-B6 cell line, respectively. We thank Dr. Gwendalyn Randolph for the use of her instruments and laboratory space for confocal imaging. We also thank the TCGA Research Network for providing data used in this publication.
Publisher 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.
PY - 2023/5
Y1 - 2023/5
N2 - AU Extramedullary: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly 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.
AB - AU Extramedullary: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly 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.
UR - http://www.scopus.com/inward/record.url?scp=85159546438&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.3001746
DO - 10.1371/journal.pbio.3001746
M3 - Article
C2 - 37134077
AN - SCOPUS:85159546438
SN - 1544-9173
VL - 21
JO - PLoS biology
JF - PLoS biology
IS - 5
M1 - e3001746
ER -