Intrinsic 5-lipoxygenase activity regulates migration and adherence of mantle cell lymphoma cells.

Autor: Xia C; Department of Medicine Solna, Division of Hematology, Karolinska University Hospital and Institutet, Stockholm, Sweden., Sadeghi L; Department of Laboratory Medicine, Division of Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden., Strååt K; Department of Medicine Solna, Division of Hematology, Karolinska University Hospital and Institutet, Stockholm, Sweden., Merrien M; Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden., Wright AP; Department of Laboratory Medicine, Division of Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden., Sander B; Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden., Xu D; Department of Medicine Solna, Division of Hematology, Karolinska University Hospital and Institutet, Stockholm, Sweden., Österborg A; Department of Medicine Solna, Division of Hematology, Karolinska University Hospital and Institutet, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Björkholm M; Department of Medicine Solna, Division of Hematology, Karolinska University Hospital and Institutet, Stockholm, Sweden., Claesson HE; Department of Medicine Solna, Division of Hematology, Karolinska University Hospital and Institutet, Stockholm, Sweden. Electronic address: hans-erik.claesson@ki.se.
Jazyk: angličtina
Zdroj: Prostaglandins & other lipid mediators [Prostaglandins Other Lipid Mediat] 2021 Oct; Vol. 156, pp. 106575. Date of Electronic Publication: 2021 Jun 08.
DOI: 10.1016/j.prostaglandins.2021.106575
Abstrakt: Human B-lymphocytes express 5-lipoxygenase (5-LOX) and 5-LOX activating protein (FLAP) and can convert arachidonic acid to leukotriene B 4 . Mantle cell lymphoma (MCL) cells contain similar amounts of 5-LOX as human neutrophils but the function and mechanism of activation of 5-LOX in MCL cells, and in normal B-lymphocytes, are unclear. Here we show that the intrinsic 5-LOX pathway in the MCL cell line JeKo-1 has an essential role in migration and adherence of the cells, which are important pathophysiological characteristics of B-cell lymphoma. Incubation of JeKo-1 with the FLAP inhibitor GSK2190915 or the 5-LOX inhibitor zileuton, at a concentration below 1 μM, prior to stimulation with the chemotactic agent CXCL12, led to a significant reduction of migration. CRISPR/Cas9 mediated deletion of ALOX5 gene in JeKo-1 cells also led to a significantly decreased migration of the cells. Furthermore, 5-LOX and FLAP inhibitors markedly decreased the adherence of JeKo-1 cells to stromal cells. In comparison, these drugs had a similar effect on adherence of JeKo-1 cells as the Bruton tyrosine kinase inhibitor ibrutinib, which has a proven anti-tumour effect. These results indicate that inhibition of 5-LOX may be a novel treatment for MCL and certain other B-cell lymphomas.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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