Department of Clinical and Biological Science, University of Turin, Orbassano, Italy.
Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
PLoS One. 2018 Jun 19;13(6):e0199371. doi: 10.1371/journal.pone.0199371. eCollection 2018.
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.
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.
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.
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.
提高血管平滑肌脂肪瘤病理生理学的认识有助于完善其药理学治疗。我们研究了血管平滑肌脂肪瘤细胞是否具有迁移特性,其生长和运动如何受激素环境的影响,以及这是否与特定性别有关。
从因治疗目的而手术切除的女性和男性患者的血管平滑肌脂肪瘤中分离出原代细胞。遗传控制显示 TSC2 无缺失。在基础条件下和在 17-β-雌二醇和 SDF-1α 的影响下,分析体外双(伤口愈合)和三维(transwell 测定)迁移。
用 17-β-雌二醇(0.1-100 nM)、他莫昔芬(0.2-20 μM)或两者联合处理长达 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-雌二醇处理诱导显著的运动增加(双维及三维),在孵育 2 小时后即可观察到。血管平滑肌脂肪瘤细胞表达编码 SDF-1α 和 17-β-雌二醇受体的 mRNA,并分泌主要参与获得恶性表型的两种金属蛋白酶,即 MMP-2 和 MMP-9。
尽管来源不同,但血管平滑肌脂肪瘤细胞的行为相似。原代血管平滑肌脂肪瘤细胞在激素环境和可溶性因子的作用下迁移,并产生活性金属蛋白酶,这两个方面都符合它们可以迁移到肺部(和/或其他器官)并在其中定植的理论。在我们分析的方面中,似乎没有主要特征与起源的性别有关。