Heparin inhibits the motility and proliferation of human myometrial and leiomyoma smooth muscle cells.
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.
Mason
Holly R
HR
Program in Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts 02114, USA.
Nowak
Romana A
RA
Morton
Cynthia C
CC
Castellot
John J
JJ
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007889:Leiomyoma / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000473:pathology; D009215:Myometrium / Q000187:drug effects / Q000473:pathology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000473:pathology
D006493:Heparin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases