title: The CD24hi smooth muscle subpopulation is the predominant fraction in uterine fibroids.
abstract: Uterine fibroids are the most common gynecological tumors affecting women in their reproductive age. Despite this high incidence the pathogenesis of fibroids is widely unsolved. Whereas formerly only imbalances in hormonal levels were considered to account for tumor development, the identification of genetic changes likely to affect myometrial stem cell reservoirs provided a novel approach to fibroid genesis. Here, we identified a certain subset of cells by the surface marker CD24 with increased abundance in fibroids compared with myometrial tissue. Fibroid cells expressing CD24 shared certain features of immature or progenitor-like cells such as quiescence, reduced expression of smooth muscle differentiation markers and elevated expression of genes involved in the wingless-type (WNT)-pathway such as beta-catenin. In addition, a positive correlation between CD24 and wingless-type family member 4 (WNT4) expression was observed in uterine fibroids with mediator subcomplex 12 gene (MED12) mutations. Our findings suggest that cells highly expressing CD24 represent a type of immature smooth muscle progenitor cells. Their accumulation might be driven by disturbed differentiation processes caused by genetic changes possibly involving MED12 mutations or high mobility group AT-hook (HMGA)2 rearrangements.
authors.affiliation: Center of Human Genetics, University of Bremen, Leobener Strasse ZHG, Bremen 28359, Germany Global Drug Discovery-TRG Oncology/Gynecological Therapies, Bayer Healthcare Pharmaceuticals, Muellerstraße 178, Berlin 13342, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Drosch
authors.affiliation: Global Drug Discovery-TRG Oncology/Gynecological Therapies, Bayer Healthcare Pharmaceuticals, Muellerstraße 178, Berlin 13342, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmidt
authors.affiliation: Global Drug Discovery-TRG Oncology/Gynecological Therapies, Bayer Healthcare Pharmaceuticals, Muellerstraße 178, Berlin 13342, Germany.
authors.forename: Dominique Nadine
authors.initials: DN
authors.lastname: Markowski
authors.affiliation: Global Drug Discovery-TRG Oncology/Gynecological Therapies, Bayer Healthcare Pharmaceuticals, Muellerstraße 178, Berlin 13342, Germany.
authors.forename: Thomas Matthias
authors.initials: TM
authors.lastname: Zollner
authors.affiliation: Global Drug Discovery-TRG Oncology/Gynecological Therapies, Bayer Healthcare Pharmaceuticals, Muellerstraße 178, Berlin 13342, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Koch
authors.affiliation: Center of Human Genetics, University of Bremen, Leobener Strasse ZHG, Bremen 28359, Germany bullerd@uni-bremen.de.
authors.forename: Jörn
authors.initials: J
authors.lastname: Bullerdiek
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D064593:Heterografts; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism*; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism; D014594:Uterine Neoplasms / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051927:CD24 Antigen; D051176:beta Catenin
keywords: cancer; leiomyoma