Background

Improving the knowledge of angiomyolipoma physiopathology might help in refining its pharmacological treatment. We investigated if angiomyolipoma cells have migratory properties, how their growth and motility can be influenced by the hormonal milieu, and if this can be related to a specific gender.

Methods

Primary cells were isolated from angiomyolipomas surgically resected for therapeutical reasons in a female and in a male patient. The genetic control demonstrated no TSC2 deletion. Bi- (wound healing) and three-dimensional (transwell assay) migration were analyzed in vitro in basal conditions and under the influence of 17- β-estradiol and SDF-1α.

Results

Treatment up to 72 hours with 17-β-estradiol (0.1–100 nM), tamoxifen (0.2–20 μM) or with both, does not modify angiomyolipoma cells proliferation. On the other hand, SDF-1α and 17-β-estradiol treatment induce a significant motility increase (both bi- and three-dimensional) which becomes evident already after 2 hours of incubation. Angiomyolipoma cells express mRNA coding for SDF-1α and 17-β-estradiol receptors and secrete both the metalloproteases principally involved in malignant phenotype acquisition, i.e. MMP-2 and MMP-9.

Conclusion

Angiomyolipoma cells behave similarly, despite their different source. Primary angiomyolipoma cells migrate in response to hormonal milieu and soluble factors, and produce active metalloproteases, both aspects being consistent with the theory claiming they can migrate to the lungs (and/or other organs) and colonizing them. No main feature, among the aspects we analyzed, seems to be referable to the gender of origin.

中文翻译：

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男性和女性来源的人肾血管平滑肌脂肪细胞可迁移并受微环境因素影响

背景

提高对血管平滑肌脂肪瘤生理病理学的了解可能有助于改善其药理学治疗方法。我们调查了血管平滑肌脂肪瘤细胞是否具有迁移特性，荷尔蒙环境如何影响它们的生长和运动，以及这是否与特定性别有关。

方法

出于治疗原因，在女性和男性患者中从手术切除的血管平滑肌脂肪瘤中分离出原代细胞。遗传对照未显示TSC2缺失。在基础条件下并在17-β-雌二醇和SDF-1α的影响下，体外分析了双向（伤口愈合）和三维（transwell分析）迁移。

结果

用17-β-雌二醇（0.1–100 nM），他莫昔芬（0.2–20μM）或同时使用这两种药物处理长达72小时，不会改变血管平滑肌脂肪瘤细胞的增殖。另一方面，SDF-1α和17-β-雌二醇处理可显着提高运动性（二维和三维），在孵育2小时后就已经很明显了。血管肌脂瘤细胞表达编码SDF-1α和17-β-雌二醇受体的mRNA，并分泌主要参与恶性表型获得的两种金属蛋白酶，即MMP-2和MMP-9。

结论

尽管来源不同，血管平滑肌脂肪瘤细胞的行为相似。原发性血管平滑肌脂肪瘤细胞响应激素环境和可溶性因子而迁移，并产生活性金属蛋白酶，这两个方面均与声称它们可以迁移至肺（和/或其他器官）并定居于其的理论相一致。在我们分析的各个方面中，没有一个主要特征似乎与原籍性别有关。