Expression patterns of leptin receptor (OB-R) isoforms and direct in vitro effects of recombinant leptin on OB-R, leptin expression and cytokine secretion by human hematopoietic malignant cells
Expression patterns of leptin receptor (OB-R) isoforms and direct in vitro effects of recombinant leptin on OB-R, leptin expression and cytokine secretion by human hematopoietic malignant cells
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DOI：
10.1016/j.cyto.2009.07.006
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发表时间：
2009-12-01
期刊：
影响因子：
3.8
通讯作者：
Georgakopoulos, Tassos
中科院分区：
文献类型：
--
作者：
Mouzaki, Athanasia;Panagoulias, Ioannis;Georgakopoulos, Tassos
已有多项研究表明瘦素与肿瘤的病理生理学有关。我们研究了瘦素对恶性造血组织的直接作用，包括：原代急性髓系白血病(AML)细胞、白血病细胞系和多发性骨髓瘤(MM)患者的骨髓活检组织。以正常人PBMC、T细胞、B细胞和单核细胞为对照。通过RT-PCP，我们确定了OB-R亚型在AML细胞和白血病细胞系中的表达模式，与对照细胞相比，Leptin上调了AML原始细胞和某些细胞系中OB-R和内源性瘦素的表达，但在对照细胞中不表达。促炎症和抗炎细胞因子的流式微珠阵列分析表明，reptin上调AML细胞分泌IL-6，受试白血病细胞株分泌各种细胞因子，单核细胞分泌IL-10。Western免疫印迹结果显示，重组瘦素的作用不依赖于JAK-2/磷酸化JAK-2蛋白水平。最后，MM活检组织的瘦素染色呈阳性，OB-R染色较少。免疫反应主要局限于骨髓瘤细胞的胞核。正常骨髓细胞、早幼粒细胞和巨核细胞呈弱阳性，红系细胞常呈阴性。我们认为瘦素/OB-R系统强烈而直接地参与支持血液系统恶性肿瘤的生长。(C)2009爱思唯尔有限公司。保留所有权利。
Several studies have implicated leptin in the pathophysiology of neoplasias. We investigated the direct effect of leptin on malignant hematopoietic tissue that included: primary acute myeloid leukemia (AML) cells, leukemic cell lines and bone marrow biopsies from multiple myeloma (MM) patients. PBMC, T-cells, B-cells and monocytes from healthy subjects served as controls. We defined the patterns of OB-R isoform expression in AML cells and leukemic cell lines in comparison to control cells by RT-PCP rLeptin upregulated the expression of OB-R and endogenous leptin in AML blasts and certain cell lines but not in control cells. Cytometric Bead Array analysis of pro- and anti-inflammatory cytokines showed that rleptin upregulates IL-6 secretion by AML cells, various cytokines by the leukemic cell lines tested and IL-10 secretion by control PBMC, contributed by monocytes. Western immunoblotting revealed that the effect of rleptin was independent of JAK-2/phospho-JAK-2 protein levels. Finally, MM biopsies stained positive for leptin and, to a lesser extend, OB-R. Immunoreactivity was confined mostly to the nucleus of the myeloma cells. Normal myelocytes, promyelocytes and megakaryocytes stained weakly positive, and erythroid cells were constantly negative. We propose that the leptin/OB-R system is strongly and directly involved in supporting the growth of hematopoietic malignancies. (C) 2009 Elsevier Ltd. All rights reserved.