title: Co-expression of CD44+/RANKL+ tumor cells in the carcinogenesis of oral squamous cell carcinoma.
abstract: Receptor activator of nuclear factor-kappa (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL) signaling helps putative cancer stem cells (CSC) to maintain their stemness. Expression of CD44 and RANKL was analyzed in oral squamous cell carcinoma specimen (n = 191). Moreover, RANKL expression was measured in cancer cell lines (BICR3, BICR56) by immunohistochemistry and western blot analysis. Scanned images were digitally analyzed using ImageJ and the immunomembrane plug-in. CD44 and RANKL expression on protein level was correlated with clinical characteristics and impact on survival. RANKL was co-labeled with CD44 in immunohistochemical and immunofluorescence double labeling experiments. Although high CD44+/RANKL+ co-expression was significantly associated with clinicopathological factors and worse survival, multivariate analysis did not demonstrate high CD44+/RANKL+ co-expression as independent prognostic factor. Immunohistochemical and immunofluorescence double labeling experiments revealed RANKL expression by CD44+ cancer cells. RANKL specificity was confirmed by western blot analysis. For the first time, this study provides evidence that RANKL expression in OSCC might be associated with disease recurrence and a cell compartment measured by CD44+/RANKL+ co-expression within the mucosal epithelial basal layer cells.
authors: Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Osianderstrasse 2-8, 72076, Tübingen, Germany, dr.dr.martingrimm@googlemail.com.
authors: Martin
authors: M
authors: Grimm
authors: Cornelius
authors: C
authors: Renz
authors: Adelheid
authors: A
authors: Munz
authors: Sebastian
authors: S
authors: Hoefert
authors: Michael
authors: M
authors: Krimmel
authors: Siegmar
authors: S
authors: Reinert
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D012680:Sensitivity and Specificity; D015398:Signal Transduction
chemical_list: D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
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