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人胆脂瘤中巨噬细胞移动抑制因子(MIF)的检测及其与复发状态、基质金属蛋白酶-3/9、视黄酸受体-β和抗凋亡半乳糖凝集素-3表达相关性的功能意义

Detection of macrophage migration inhibitory factor (MIF) in human cholesteatomas and functional implications of correlations to recurrence status and to expression of matrix metalloproteinases-3/9, retinoic acid receptor-beta, and anti-apoptotic galectin-3.

作者信息

Choufani G, Ghanooni R, Decaestecker C, Delbrouck K, Simon P, Schüring M P, Zick Y, Hassid S, Gabius H J, Kiss R

机构信息

Department of Otolaryngology & Head and Neck Surgery, Erasmus University Hospital, Brussels, Belgium.

出版信息

Laryngoscope. 2001 Sep;111(9):1656-62. doi: 10.1097/00005537-200109000-00031.

DOI:10.1097/00005537-200109000-00031
PMID:11568623
Abstract

OBJECTIVES

To investigate whether the expression of the macrophage migration inhibitory factor (MIF) 1) is detectable, 2) changes in relation to recurrence and infection status, and 3) relates to the levels of expression of growth regulators/differentiation markers, including galectin-1, -3, and -8, retinoid acid receptors (RAR)]-alpha, -beta, and -gamma, binding sites for sarcolectin, and invasion markers (cathepsins -B and -D, and matrix metalloproteinases [MMP]-2, -3, and -9) in human cholesteatomas.

STUDY DESIGN

An analysis of 56 cholesteatomas resected by the same surgeon using canal wall up and canal wall down surgical procedures.

METHODS

The immunohistochemical levels of expression of MIF and the proteases were quantitatively determined (using computer-assisted microscopy) on routine histologic slides by specific antibodies, and statistically correlated to parameters of the other markers determined previously in conjunction with data on apoptosis/proliferation.

RESULTS

MIF expression was detected. It was significantly higher in the epithelium (P =.002) and vessels (P =.04) of the connective tissues (but not in the connective tissue itself) of recurrent as opposed to non-recurrent cholesteatomas. The MIF expression is significantly correlated (P =.006) to the RAR beta expression in non-infected cholesteatomas, and to MMP-3 (P <.01) and anti-apoptotic galectin-3 (P =.01) in infected cholesteatomas. The level of MIF expression was also correlated significantly to MMP-9 (P = 0.003), RAR beta (P <.001), and galectin-8 (P =.003) expression in the cholesteatomas regardless of their infection status.

CONCLUSIONS

MIF expression in human cholesteatomas is related to the levels of biologic aggressiveness reflected in their recurrence status and MMP expression, and to the differentiation status reflected in their galactin and RAR beta expressions. Together with galectin-3, it could cooperate to form an anti-apoptotic feedback loop.

摘要

目的

研究巨噬细胞移动抑制因子(MIF)的表达情况:1)是否可检测到;2)与复发和感染状态相关的变化;3)与生长调节因子/分化标志物的表达水平的关系,这些标志物包括半乳糖凝集素-1、-3和-8、视黄酸受体(RAR)-α、-β和-γ、肌集钙蛋白结合位点以及侵袭标志物(组织蛋白酶-B和-D、基质金属蛋白酶[MMP]-2、-3和-9)在人胆脂瘤中的表达情况。

研究设计

对同一位外科医生采用外耳道壁上和外耳道壁下手术方法切除的56例胆脂瘤进行分析。

方法

通过特异性抗体在常规组织学切片上定量测定(使用计算机辅助显微镜)MIF和蛋白酶的免疫组化表达水平,并与先前测定的其他标志物参数以及凋亡/增殖数据进行统计学关联。

结果

检测到MIF表达。与非复发性胆脂瘤相比,复发性胆脂瘤结缔组织的上皮(P = 0.002)和血管(P = 0.04)中的MIF表达显著更高(但结缔组织本身中无此现象)。在未感染的胆脂瘤中,MIF表达与RARβ表达显著相关(P = 0.006),在感染的胆脂瘤中与MMP-3(P < 0.01)和抗凋亡半乳糖凝集素-3(P = 0.01)显著相关。无论感染状态如何,胆脂瘤中MIF表达水平也与MMP-9(P = 0.003)、RARβ(P < 0.001)和半乳糖凝集素-8(P = 0.003)表达显著相关。

结论

人胆脂瘤中的MIF表达与复发状态和MMP表达所反映的生物学侵袭性水平以及半乳糖凝集素和RARβ表达所反映的分化状态相关。与半乳糖凝集素-3一起,它可能协同形成一个抗凋亡反馈环。

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