Mason Holly R, Nowak Romana A, Morton Cynthia C, Castellot John J
Program in Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts 02114, USA.
Am J Pathol. 2003 Jun;162(6):1895-904. doi: 10.1016/S0002-9440(10)64323-4.
Uterine fibroids (leiomyomas) are a major women's health problem. Currently, the standard for treatment remains hysterectomy, because no other treatment modalities can reduce both symptoms and recurrence. As leiomyomas are a hyperproliferation of smooth muscle cells, we sought to understand the regulation of uterine smooth muscle cell mitogenesis by the glycosaminoglycan heparin, which has been extensively studied as an anti-proliferative molecule in vascular smooth muscle cells. Using matched pairs of human myometrial and leiomyoma smooth muscle cells from the same uterus, we demonstrate that the proliferation and motility of both cell types are inhibited by heparin. We report that the decrease in cell number seen in the presence of heparin is not because of cell death. Interestingly, there is significant patient-to-patient variability in the proliferation response but not in the motility response to heparin. Furthermore, nonanticoagulant and anticoagulant heparin were equally effective at inhibiting leiomyoma and myometrial smooth muscle cell proliferation. These results warrant further investigation into the possibility that heparin might be useful in the treatment of uterine fibroids.
子宫肌瘤是一个主要的女性健康问题。目前,治疗的标准仍然是子宫切除术,因为没有其他治疗方式能够同时减轻症状和降低复发率。由于子宫肌瘤是平滑肌细胞的过度增殖,我们试图了解糖胺聚糖肝素对子宫平滑肌细胞有丝分裂的调节作用,肝素作为一种抗增殖分子,已在血管平滑肌细胞中得到广泛研究。使用来自同一子宫的配对的人子宫肌层和平滑肌瘤平滑肌细胞,我们证明肝素可抑制这两种细胞类型的增殖和运动。我们报告称,在肝素存在的情况下观察到的细胞数量减少并非由于细胞死亡。有趣的是,肝素对细胞增殖反应存在显著的个体差异,但对细胞运动反应则没有。此外,非抗凝肝素和抗凝肝素在抑制子宫肌瘤和平滑肌瘤平滑肌细胞增殖方面同样有效。这些结果值得进一步研究肝素可能用于治疗子宫肌瘤的可能性。