title: Why leiomyomas are called fibroids: the central role of extracellular matrix in symptomatic women.
abstract: Uterine leiomyomas are highly prevalent and symptomatic tumors of women in their reproductive years. The morbidity caused by these tumors is directly related to increasing size. Leiomyoma cells do not rapidly proliferate; instead, the tumors grow primarily due to excessive production of disorganized extracellular matrix (ECM). The aberrant ECM results from excessive production of collagen subtypes and proteoglycans, increased profibrotic cytokines including transforming growth factors beta1 and beta3, and decreased or disrupted matrix metalloproteinases. These alterations result in the development of an ECM that is exceptionally stable. As a result, therapeutic interventions must redirect leiomyoma cells toward extracellular matrix dissolution, rather than solely inhibiting cell proliferation. Gonadotropin-releasing hormone analogues and selective progesterone receptor modulators with demonstrated clinical efficacy provide such a change in abnormal extracellular matrix formation by leiomyoma cells, inhibiting and reversing the fibrotic process. Novel therapies using pathways distinct from gonadal hormones, including antifibrotics, retinoic acid, peroxisome-proliferator-activated receptor gamma ligands, and curcumin, provide promise for a future with improved therapeutic options for women suffering from uterine leiomyomas.
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814-4799, USA.
authors.forename: Minnie
authors.initials: M
authors.lastname: Malik
authors.forename: John
authors.initials: J
authors.lastname: Norian
authors.forename: Desirée
authors.initials: D
authors.lastname: McCarthy-Keith
authors.forename: Joy
authors.initials: J
authors.lastname: Britten
authors.forename: William H
authors.initials: WH
authors.lastname: Catherino
mesh_terms: D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006728:Hormones / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007889:Leiomyoma / Q000453:epidemiology / Q000378:metabolism* / Q000628:therapy; D020782:Matrix Metalloproteinases / Q000378:metabolism; D015995:Prevalence; D011509:Proteoglycans / Q000378:metabolism; D012106:Research / Q000639:trends; D009626:Terminology as Topic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014594:Uterine Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000628:therapy
chemical_list: D006728:Hormones; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D003094:Collagen; D020782:Matrix Metalloproteinases