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CD147和基质金属蛋白酶-2在转移性和非转移性葡萄膜黑色素瘤中的表达

CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas.

作者信息

Lüke Julia, Vukoja Vlatka, Brandenbusch Tim, Nassar Khaled, Rohrbach Jens Martin, Grisanti Salvatore, Lüke Matthias, Tura Aysegül

机构信息

Department of Ophthalmology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.

University Eye Hospital, Centre of Ophthalmology, Eberhard-Karls University of Tuebingen, Tuebingen, Germany.

出版信息

BMC Ophthalmol. 2016 Jun 3;16:74. doi: 10.1186/s12886-016-0222-4.

Abstract

BACKGROUND

Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis.

METHODS

The expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression).

RESULTS

CD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non-metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident.

CONCLUSIONS

These data may indicate that CD147 regulates MMP-2 expression in uveal melanoma cells.

摘要

背景

由基质金属蛋白酶(MMP)诱导剂(CD147)调节的细胞外基质重塑是肿瘤细胞侵袭和血液供应调节过程中的关键环节。在本研究中,我们评估了CD147和MMP - 2表达与葡萄膜黑色素瘤主要预后因素及转移发生之间的相关性。

方法

对49例葡萄膜黑色素瘤样本进行CD147和MMP - 2表达分析。使用针对神经胶质细胞(GFAP)、内皮细胞(CD34)和巨噬细胞(CD68)的标志物进行三重免疫荧光染色,以进一步分析CD147和MMP - 2阳性的确切定位。28例患者出现临床转移性疾病。其余21例患者平均随访10年未显示转移疾病迹象。进行相关性分析(Pearson相关性分析),以分析CD147和MMP - 2表达与已知预后因素、血管生成拟态(VM)、成熟血管系统(血管性血友病因子)和肿瘤诱导的血管生成(通过内皮糖蛋白表达)之间的关联。

结果

47例(96.0%)葡萄膜黑色素瘤表达CD147和MMP - 2。CD147上调与较高的MMP - 2表达显著相关。整体表达分析显示转移性亚组(p = 0.777)和非转移性亚组(p = 0.585)之间无显著差异。CD147表达与任何血液供应系统均无明显相关性。在非转移性亚组中,聚集的CD147阳性细胞与最大基底直径(p = 0.039)、高度(p = 0.047)和TNM分期(p = 0.013)之间存在显著相关性。

结论

这些数据可能表明CD147调节葡萄膜黑色素瘤细胞中MMP - 2的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a51e/4891917/10dc4d251b1c/12886_2016_222_Fig1_HTML.jpg

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