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[微环境对眼内黑色素瘤与皮下黑色素瘤血管生成拟态影响的机制]

[The mechanisms of microenvironments influence on vasculogenic mimicry between intraocular and subcutaneous melanoma].

作者信息

Chen Lu-Xia, Sun Bao-Cun, Zhang Shi-Wu, He Yan-Jin, Li Xiao-Rong, He Zhong-Jiang

机构信息

Eye Center of Tianjin Medical University, Tianjin 300070, China.

出版信息

Zhonghua Yan Ke Za Zhi. 2009 Jul;45(7):641-6.

PMID:19957694
Abstract

OBJECTIVE

To investigate the influence of different microenvironments on melanoma vasculogenic mimicry, invasiveness and metastasis behavior.

METHODS

It was an experimental study. Sixty C57BL/6J mice were randomly divided into two groups with 30 mice per group. Melanoma B16 cells were injected into the subretinal space and groin area of mice synchronously. The number of each type of microcirculation pattern was counted. The invasion and metastasis were observed. EphA2, MMP-2 and MMP-9 expression and their mRNA levels were detected by immunohistochemical staining and real time RT-PCR and compared between two groups.

RESULTS

Five invasions and six lung metastases were found in the subretinal group while no invasion and metastasis were found in the groin group. The number of VM channels was significantly higher in subretinal group (t = 4. 188, P = 0.000). However, no significant difference of mosaic vessel and endothelium-dependent vessel was observed between two groups (t = 1.473, 1.805; P = 0.146, 0.076, respectively). EphA2, MMP-2 and MMP-9 expression was significantly higher in the subretinal group (data not shown). The mRNA levels of EphA2, MMP-2 and MMP-9 were rather higher in the subretinal tumor (t = 3.642, 8.109, 9.357; P = 0.002, 0.001 and 0.001, respectively). There was a positive association in melanoma cells of the VM between expression of EphA2 (r = 0.412, P = 0.021) but no statistically significant correlation between VM and MMP-2 (P > 0.05), nor between VM and MMP-9.

CONCLUSIONS

Different microenvironments affect invasiveness and blood supply patterns of melanoma. Melanoma cells in intraocular microenvironment increased EphA2 expression which induced the formation of VM channels. Moreover, the expression of MMP-2 and MMP-9 in tumor tissue increased to enhance the invasiveness and metastasis behavior.

摘要

目的

探讨不同微环境对黑色素瘤血管生成拟态、侵袭及转移行为的影响。

方法

本研究为实验性研究。将60只C57BL/6J小鼠随机分为两组,每组30只。将黑色素瘤B16细胞同步注射到小鼠的视网膜下间隙和腹股沟区。计数每种微循环模式的数量。观察侵袭和转移情况。采用免疫组织化学染色和实时RT-PCR检测EphA2、MMP-2和MMP-9的表达及其mRNA水平,并在两组之间进行比较。

结果

视网膜下组发现5处侵袭和6处肺转移,而腹股沟组未发现侵袭和转移。视网膜下组的VM通道数量显著更高(t = 4.188,P = 0.000)。然而,两组之间的镶嵌血管和内皮依赖性血管无显著差异(t = 1.473,1.805;P分别为0.146,0.076)。视网膜下组EphA2、MMP-2和MMP-9的表达显著更高(数据未显示)。视网膜下肿瘤中EphA2、MMP-2和MMP-9的mRNA水平更高(t = 3.642,8.109,9.357;P分别为0.002,0.001和0.001)。黑色素瘤细胞的VM中EphA2表达之间存在正相关(r = 0.412,P = 0.021),但VM与MMP-2之间无统计学显著相关性(P > 0.05),VM与MMP-9之间也无相关性。

结论

不同微环境影响黑色素瘤的侵袭性和血液供应模式。眼内微环境中的黑色素瘤细胞增加了EphA2表达,从而诱导VM通道的形成。此外,肿瘤组织中MMP-2和MMP-9的表达增加,以增强侵袭和转移行为。

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