title: Proteoglycans in Leiomyoma and Normal Myometrium: Abundance, Steroid Hormone Control, and Implications for Pathophysiology.
abstract: Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA Seattle Reproductive Medicine, North Seattle, WA, USA.
authors.forename: Nichole M
authors.initials: NM
authors.lastname: Barker
authors.affiliation: Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH, USA Department of Chemistry, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Carrino
authors.affiliation: Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Caplan
authors.affiliation: Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA Duke Fertility Center, Durham, NC, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Hurd
authors.affiliation: Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA sam.mesiano@case.edu.
authors.forename: Sam
authors.initials: S
authors.lastname: Mesiano
mesh_terms: D000328:Adult; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D058575:Decorin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011374:Progesterone / Q000494:pharmacology; D011397:Promegestone / Q000494:pharmacology; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000503:physiopathology
chemical_list: C546878:DCN protein, human; D058575:Decorin; D011509:Proteoglycans; D011374:Progesterone; D004958:Estradiol; D011397:Promegestone
keywords: leiomyoma; proteoglycans; steroid hormones