title: Mouse 3T3 fibroblasts under the influence of fibroblasts isolated from stroma of human basal cell carcinoma acquire properties of multipotent stem cells.
abstract: BACKGROUND
  Multipotent mesenchymal stem cells can participate in the formation of a microenvironment stimulating the aggressive behaviour of cancer cells. Moreover, cells exhibiting pluripotent ESC (embryonic stem cell) markers (Nanog and Oct4) have been observed in many tumours. Here, we investigate the role of cancer-associated fibroblasts in the formation of stem cell supporting properties of tumour stroma. We test the influence of fibroblasts isolated from basal cell carcinoma on mouse 3T3 fibroblasts, focusing on the expression of stem cell markers and plasticity in vitro by means of microarrays, qRT-PCR (quantitative real-time PCR) and immunohistochemistry.
  
  
  RESULTS
  We demonstrate the biological activity of the cancer stromal fibroblasts by influencing the 3T3 fibroblasts to express markers such as Oct4, Nanog and Sox2 and to show differentiation potential similar to mesenchymal stem cells. The role of growth factors such as IGF2 (insulin-like growth factor 2), FGF7 (fibroblast growth factor 7), LEP (leptin), NGF (nerve growth factor) and TGFβ (transforming growth factor β), produced by the stromal fibroblasts, is established to participate in their bioactivity. Uninduced 3T3 do not express the stem cell markers and show minimal differentiation potential.
  
  
  CONCLUSIONS
  Our observations indicate the pro-stem cell activity of cancer-associated fibroblasts and underline the role of epithelial-mesenchymal interaction in tumour biology.
authors.affiliation: Institute of Anatomy, First Faculty of Medicine, Charles University in Prague, U Nemocnice 3, CZ-12800 Prague 2, Czech Republic.
authors.forename: Pavol
authors.initials: P
authors.lastname: Szabó
authors.forename: Michal
authors.initials: M
authors.lastname: Kolář
authors.forename: Barbora
authors.initials: B
authors.lastname: Dvořánková
authors.forename: Lukáš
authors.initials: L
authors.lastname: Lacina
authors.forename: Jiří
authors.initials: J
authors.lastname: Štork
authors.forename: Čestmír
authors.initials: Č
authors.lastname: Vlček
authors.forename: Hynek
authors.initials: H
authors.lastname: Strnad
authors.forename: Miroslav
authors.initials: M
authors.lastname: Tvrdek
authors.forename: Karel
authors.initials: K
authors.lastname: Smetana
mesh_terms: D016475:3T3 Cells; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000473:pathology*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D039902:Multipotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor