title: SOX2 expression associates with stem cell state in human ovarian carcinoma.
abstract: The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC.
authors.affiliation: Departments of Internal Medicine II and Preclinical Imaging and Radiopharmacy, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, University of Tuebingen, Tuebingen, Germany.
authors.forename: Petra M
authors.initials: PM
authors.lastname: Bareiss
authors.forename: Anna
authors.initials: A
authors.lastname: Paczulla
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Rebekka
authors.initials: R
authors.lastname: Schairer
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
authors.forename: Ursula
authors.initials: U
authors.lastname: Kohlhofer
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Rothfuss
authors.forename: Anna
authors.initials: A
authors.lastname: Fischer
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Bernd
authors.initials: B
authors.lastname: Pichler
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Frank
authors.initials: F
authors.lastname: Essmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Lengerke
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D016688:Mice, Inbred NOD; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2