المؤلفون: Barisas, Derek A. G., Kabir, Ashraf Ul, Wu, Jun, Krchma, Karen, Kim, Minseo, Subramanian, Madhav, Zinselmeyer, Bernd H., Stewart, Colin L., Choi, Kyunghee

المصدر: PLoS Biology; 5/3/2023, Vol. 21 Issue 5, p1-28, 28p, 1 Diagram, 6 Graphs

مصطلحات موضوعية: EXTRAMEDULLARY hematopoiesis, LEUKEMIA inhibitory factor, HEMATOPOIETIC stem cells, COOPERATIVE binding (Biochemistry), HEMATOPOIESIS, MYELOID cells

مستخلص: 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. [ABSTRACT FROM AUTHOR]

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المؤلفون: Seo, Yohan, Park, Jinhong, Kim, Minseo, Lee, Ho K., Kim, Jin-Hee, Jeong, Jin-Hyun, Namkung, Wan

المصدر: PLoS ONE; 7/21/2015, Vol. 10 Issue 7, p1-15, 15p

مصطلحات موضوعية: CHLORIDE channels, CELL-mediated cytotoxicity, CANCER cell culture, ENZYME inhibitors, CANCER cell proliferation, CYCLIC-AMP-dependent protein kinase

مستخلص: The expression levels of anoctamin 1 (ANO1, TMEM16A), a calcium-activated chloride channel (CaCC), are significantly increased in several tumors, and inhibition of ANO1 is known to reduce cell proliferation and migration. Here, we performed cell-based screening of a collection of natural products and drug-like compounds to identify inhibitors of ANO1. As a result of the screening, idebenone, miconazole and plumbagin were identified as novel ANO1 inhibitors. Electrophysiological studies showed that idebenone, a synthetic analog of coenzyme Q10, completely blocked ANO1 activity in FRT cells expressing ANO1 without any effect on intracellular calcium signaling and CFTR, a cAMP-regulated chloride channel. The CaCC activities in PC-3 and CFPAC-1 cells expressing abundant endogenous ANO1 were strongly blocked by idebenone. Idebenone inhibited cell proliferation and induced apoptosis in PC-3 and CFPAC-1 cells, but not in A549 cells, which do not express ANO1. These data suggest that idebenone, a novel ANO1 inhibitor, has potential for use in cancer therapy. [ABSTRACT FROM AUTHOR]

: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)