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基因表达分析显示子宫平滑肌瘤假包膜中存在血管生成特征。

Gene expression analysis reveals an angiogenic profile in uterine leiomyoma pseudocapsule.

机构信息

Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.

出版信息

Mol Hum Reprod. 2013 Jun;19(6):380-7. doi: 10.1093/molehr/gat007. Epub 2013 Jan 25.

DOI:10.1093/molehr/gat007
PMID:23355533
Abstract

The pseudocapsule (PC) of the uterine leiomyoma (UL) is an anatomic entity that surrounds the myoma separating it from the myometrium (UM). Although a number of microarray experiments have identified differences in gene expression profile in the UL when compared with the UM, there is a lack of systematic studies on the PC. In this study, quantitative RT-PCR analysis was performed on 18 matched PC, UL and UM specimens and results showed that the PC displays a specific gene expression profile. The low expression level of insulin-like growth factor (IGF-2), a fibroid specific marker, that we found in the PC and the UM when compared with the UL, clearly indicates that the PC is in structural continuity with the UM. However, the significant increase in endoglin expression level in PC with respect to the UL and UM indicates that an active neoangiogenesis is present in PC. Conversely, other angiogenic factors such as von Willebrand factor (vWF) and vascular endothelial growth factor A (VEGF-A) seem to have little influence on the PC angiogenesis. Because the endoglin is preferentially expressed in proliferating endothelial cells, whereas the vWF and VEGF-A are preferentially expressed in preexisting endothelial cells, our idea is that the angiogenic activity in the PC is linked to wound healing. The angiogenic activity is also sustained by intermediate expression level of cystein-rich angiogenesis inducer 61, connective tissue growth factor and collagen 4α2 genes all involved in the neoangiogenesis, that we detected in the PC. Taken together our data demonstrate that the specific expression pattern observed in the PC could be the response of the uterine wall's smooth cells to the tension imposed by the tumor. As a consequence, a neovascular structure is generated involving regenerative processes. For these reasons, we suggest that the laparoscopic intracapsular myomectomy (LIM), a new surgical technique that preserves the PC during the UL removal, should always be preferred, to favor a faster and proper uterine healing.

摘要

子宫肌瘤的假包膜(PC)是一种解剖实体,环绕着肌瘤,将其与子宫肌层(UM)隔开。尽管许多微阵列实验已经确定了与 UM 相比 UL 中基因表达谱的差异,但对于 PC 缺乏系统的研究。在这项研究中,对 18 个匹配的 PC、UL 和 UM 标本进行了定量 RT-PCR 分析,结果表明 PC 显示出特定的基因表达谱。我们发现 PC 和 UM 中胰岛素样生长因子(IGF-2)的低表达水平,这是一种特定于纤维瘤的标志物,明显表明 PC 与 UM 在结构上是连续的。然而,PC 中内皮糖蛋白表达水平的显著增加与 UL 和 UM 相比,表明 PC 中存在活跃的新生血管生成。相反,其他血管生成因子,如血管性血友病因子(vWF)和血管内皮生长因子 A(VEGF-A)似乎对 PC 血管生成影响不大。由于内皮糖蛋白优先在增殖的内皮细胞中表达,而 vWF 和 VEGF-A 优先在预先存在的内皮细胞中表达,我们的想法是 PC 中的血管生成活性与伤口愈合有关。PC 中检测到的富含半胱氨酸的血管生成诱导因子 61、结缔组织生长因子和胶原 4α2 等基因的中间表达水平也维持了血管生成活性,这些基因都参与了新生血管生成。综上所述,我们的数据表明,PC 中观察到的特定表达模式可能是子宫壁平滑肌细胞对肿瘤施加的张力的反应。因此,产生了一种涉及再生过程的新血管结构。出于这些原因,我们建议保留 PC 的腹腔镜囊内子宫肌瘤切除术(LIM),应始终优先选择这种新的手术技术,以促进更快和适当的子宫愈合。

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