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[胰岛素样生长因子-1、血管内皮生长因子、白细胞介素-6在多发性骨髓瘤进展中的意义]

[The significance of IGF-1, VEGF, IL-6 in multiple myeloma progression].

作者信息

Guo Yi-qun, Chen Shi-lun

机构信息

Department of Hematology, Chao Yang Hospital, Capital University of Medical Science, Beijing 100020, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2006 Apr;27(4):231-4.

PMID:16875552
Abstract

OBJECTIVE

To study the alteration and significance of IL-6, vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1) in MM progression and the interaction between the three cytokines.

METHODS

Bone marrow samples from 28 patients with multiple myeloma (MM) (evolution group and steady group), 10 iron deficiency anemia (as normal control) and 2 monoclonal gammopathy of undetermined significance (MGUS) were studied. Bone marrow stromal cells (BMSCs) were established from the bone marrow MNCs. ELISA was performed to detect the concentration of IL-6, VEGF, IGF-1 in culture supernates.

RESULTS

(1) The levels of IL-6 and VEGF secreted by BMSCs were increased in an order from normal control to steady group to evolution group (P < 0.05). However, the concentration of IGF-1 did not increase in MM patients (P > 0.05). (2) The levels of IL-6, VEGF and IGF-1 in the coculture supernates of U266 and BMSCs were increased significantly (P < 0.05), being in an ascending order from normal control to steady group to evolution group (P < 0.05). (3) BMSCs stimulated by exogenous IL-6, VEGF or IGF-1, secreted more VEGF, IGF-1/IL-6, IGF-1/VEGF, IL-6 than unstimulated (P < 0.05). (4) The levels of IL-6, VEGF, IGF-1 secreted by BMSCs from MGUS were similar to that from control group.

CONCLUSIONS

IL-6, VEGF, IGF-1 levels associate with evolution of MM; IL-6, VEGF and IGF-1 induce an increase in cytokines secretion of BMSCs.

摘要

目的

研究白细胞介素-6(IL-6)、血管内皮生长因子(VEGF)、胰岛素样生长因子-1(IGF-1)在多发性骨髓瘤(MM)进展中的变化及其意义,以及这三种细胞因子之间的相互作用。

方法

研究了28例多发性骨髓瘤患者(进展组和稳定组)、10例缺铁性贫血患者(作为正常对照)和2例意义未明的单克隆丙种球蛋白病(MGUS)患者的骨髓样本。从骨髓单个核细胞中分离培养骨髓基质细胞(BMSCs)。采用酶联免疫吸附测定(ELISA)法检测培养上清液中IL-6、VEGF、IGF-1的浓度。

结果

(1)BMSCs分泌的IL-6和VEGF水平从正常对照到稳定组再到进展组呈递增趋势(P<0.05)。然而,MM患者的IGF-1浓度并未升高(P>0.05)。(2)U266与BMSCs共培养上清液中IL-6、VEGF和IGF-1水平显著升高(P<0.05),从正常对照到稳定组再到进展组呈递增趋势(P<0.05)。(3)外源性IL-6、VEGF或IGF-1刺激的BMSCs分泌的VEGF、IGF-1/IL-6、IGF-1/VEGF、IL-6比未刺激的更多(P<0.05)。(4)MGUS患者BMSCs分泌的IL-6、VEGF、IGF-1水平与对照组相似。

结论

IL-6、VEGF、IGF-1水平与MM的进展相关;IL-6、VEGF和IGF-1可诱导BMSCs细胞因子分泌增加。

相似文献

1
[The significance of IGF-1, VEGF, IL-6 in multiple myeloma progression].[胰岛素样生长因子-1、血管内皮生长因子、白细胞介素-6在多发性骨髓瘤进展中的意义]
Zhonghua Xue Ye Xue Za Zhi. 2006 Apr;27(4):231-4.
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[The interaction of vascular endothelial growth factor and interleukin-6 in multiple myeloma].[血管内皮生长因子与白细胞介素-6在多发性骨髓瘤中的相互作用]
Zhonghua Nei Ke Za Zhi. 2005 Feb;44(2):85-8.
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[Clinical significance of serum vascular endothelial growth factor and interleukin-6 in multiple myeloma].血清血管内皮生长因子和白细胞介素-6在多发性骨髓瘤中的临床意义
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2005 Feb;30(1):68-71.
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Clin Cancer Res. 2006 Oct 1;12(19):5887-94. doi: 10.1158/1078-0432.CCR-05-2501.
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Transforming growth factor beta receptor I kinase inhibitor down-regulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment.转化生长因子β受体I激酶抑制剂可下调骨髓微环境中细胞因子的分泌并抑制多发性骨髓瘤细胞生长。
Clin Cancer Res. 2004 Nov 15;10(22):7540-6. doi: 10.1158/1078-0432.CCR-04-0632.
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[Influence of thalidomide on bone marrow microenvironment in refractory and relapsed multiple myeloma].[沙利度胺对难治性及复发性多发性骨髓瘤骨髓微环境的影响]
Ai Zheng. 2003 Apr;22(4):346-9.
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[Both myeloma cells and bone marrow stromal cells are involved in the overproduction of interleukin 6 in multiple myeloma].骨髓瘤细胞和骨髓基质细胞均参与多发性骨髓瘤中白细胞介素6的过度产生。
Zhonghua Xue Ye Xue Za Zhi. 1998 Jun;19(6):306-8.
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The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma.对于难治性/复发性多发性骨髓瘤患者,中等剂量沙利度胺与地塞米松联合使用可降低骨髓微血管密度,但不会降低血管生成细胞因子的血清水平。
Hematol Oncol. 2004 Dec;22(4):159-68. doi: 10.1002/hon.738.
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Kynurenic acid in blood and bone marrow plasma of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients.不明意义单克隆丙种球蛋白血症(MGUS)和多发性骨髓瘤(MM)患者血液和骨髓血浆中的犬尿氨酸酸。
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IGF-1, IGFBP-3, VEGF and MMP-9 levels and their potential relationship with renal functions in patients with compensatory renal growth.代偿性肾生长患者中IGF-1、IGFBP-3、VEGF和MMP-9水平及其与肾功能的潜在关系。
Clin Physiol Funct Imaging. 2008 Mar;28(2):107-12. doi: 10.1111/j.1475-097X.2007.00783.x. Epub 2007 Dec 18.

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J Hematol Oncol. 2014 Jan 15;7:9. doi: 10.1186/1756-8722-7-9.
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Inhibition of IGF-1 signalling enhances the apoptotic effect of AS602868, an IKK2 inhibitor, in multiple myeloma cell lines.抑制 IGF-1 信号通路增强了 IKK2 抑制剂 AS602868 在多发性骨髓瘤细胞系中的凋亡作用。
PLoS One. 2011;6(7):e22641. doi: 10.1371/journal.pone.0022641. Epub 2011 Jul 25.