Tumor-derived interleukin-1α and leukemia inhibitory factor promote extramedullary hematopoiesis.
Tumor-derived interleukin-1α and leukemia inhibitory factor promote extramedullary hematopoiesis.
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DOI：
10.1371/journal.pbio.3001746
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发表时间：
2023-05
期刊：
影响因子：
9.8
通讯作者：
Choi, Kyunghee
中科院分区：
文献类型：
--
作者：
Barisas, Derek A. G.;Ul Kabir, Ashraf;Wu, Jun;Krchma, Karen;Kim, Minseo;Subramanian, Madhav;Zinselmeyer, Bernd H. H.;Stewart, Colin L. L.;Choi, Kyunghee
髓外造血（EMH）扩大骨髓外的造血能力，以响应炎症条件，包括感染和癌症。由于其可诱导的性质，EMH提供了一个独特的机会，研究造血干细胞和祖细胞（HSPCs）和他们的生态位之间的相互作用。在癌症患者中，脾脏经常充当EMH器官，并提供可能使病理恶化的骨髓细胞。在这里，我们研究了HSPCs和它们的脾脏生态位在EMH小鼠乳腺癌模型之间的关系。我们鉴定了肿瘤产生的IL-1α和白血病抑制因子（LIF）分别作用于脾HSPCs和脾龛细胞。IL-1α诱导脾HSPCs表达TNFα，激活脾龛活性，LIF诱导脾龛细胞增殖。IL-1α和LIF在激活EMH中显示协同作用，并且在一些人类癌症中均上调。总之，这些数据扩展了开发利基导向疗法的途径，并进一步探索EMH伴随的炎症病理学，如癌症。这项研究表明，肿瘤产生的IL-1α和LIF促进髓外造血。LIF直接扩增脾小生境细胞，而IL-1α诱导造血干细胞和祖细胞产生TNFα以激活脾小生境细胞;两者均扩增骨髓偏向的脾造血。
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. This study shows that tumor-produced IL-1α and LIF promote extramedullary hematopoiesis. LIF directly expands splenic niche cells while IL-1α induces TNFα production in hematopoietic stem and progenitor cells to activate splenic niche cells; both expand myeloid-biased splenic hematopoiesis.
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影响因子：
12.8
作者：
Fan N;Lavu S;Hanson CA;Tefferi A
通讯作者：
Tefferi A
DOI：
10.1073/pnas.1113744109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Cortez-Retamozo, Virna;Etzrodt, Martin;Pittet, Mikael J.
通讯作者：
Pittet, Mikael J.
DOI：
10.1093/rheumatology/keq031
发表时间：
2010-07
期刊：
Rheumatology (Oxford, England)
影响因子：
--
作者：
Horiuchi T;Mitoma H;Harashima S;Tsukamoto H;Shimoda T
通讯作者：
Shimoda T
影响因子：
5.3
作者：
GUY, CT;CARDIFF, RD;MULLER, WJ
通讯作者：
MULLER, WJ
影响因子：
3.3
作者：
Bao Y;Liu Z;Guo M;Li B;Sun X;Wang L
通讯作者：
Wang L