Intrinsic 5-lipoxygenase activity regulates migration and adherence of mantle cell lymphoma cells
| Autor: | Klas Strååt, Magali Merrien, Anders Österborg, Anthony P. H. Wright, Laia Sadeghi, Magnus Björkholm, Chuanyou Xia, Birgitta Sander, Dawei Xu, Hans-Erik Claesson |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pharmacology Stromal cell biology Physiology Chemistry Leukotriene B4 Chemotaxis Lymphoma Mantle-Cell Cell Biology 030204 cardiovascular system & hematology medicine.disease Biochemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Cell culture Ibrutinib Arachidonate 5-lipoxygenase biology.protein Cancer research medicine Bruton's tyrosine kinase Mantle cell lymphoma |
| Zdroj: | Prostaglandins & Other Lipid Mediators. 156:106575 |
| ISSN: | 1098-8823 |
| Popis: | Human B-lymphocytes express 5-lipoxygenase (5-LOX) and 5-LOX activating protein (FLAP) and can convert arachidonic acid to leukotriene B4. 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. |
| Databáze: | OpenAIRE |
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