title: Stromal fibroblasts from basal cell carcinoma affect phenotype of normal keratinocytes.
abstract: BACKGROUND
  Epithelial-mesenchymal interactions are important not only to direct the course of prenatal development of skin and its appendages but also to influence the behaviour of transformed epithelial cells.
  
  
  OBJECTIVE
  Evaluation of the role of stromal fibroblasts on the phenotype of epithelial cells of basal cell carcinoma (BCC).
  
  
  METHODS
  The phenotype of human BCC was compared with the in vitro model where the growth and phenotypic pattern of normal human keratinocytes were monitored in co-culture with fibroblasts prepared from stroma of BCC (BCCFs), with normal dermal fibroblasts or with two established fibroblast lines. We visualized the expression of a panel of keratins, three types of endogenous lectin [galectin (Gal)-1, Gal-3 and Gal-7], binding sites for Gal-1 and Gal-3, a proliferation marker Ki67, nucleolar protein nucleostemin (NuclS) and membrane protein Ber-EP4. A phenotype and karyotype of BCCFs were also monitored. BCCFs were also grafted to NOD/LtSz-Rag1(null) mice to evaluate their malignant potential.
  
  
  RESULTS
  Prolonged cultivation of BCCFs has led to morphological changes, loss of contact inhibition, loss of fibroblast surface antigens and progressive aneuploidity. However, a fully malignant phenotype did not develop as these cells did not form tumours in immunodeficient mice. Co-culture of BCCFs with normal keratinocytes in vitro led to their phenotypical changes resembling those in BCC, namely, expression of keratin 19. These keratinocytes also strongly express nuclear binding sites for Gal-1 and NuclS. This phenotype was not observed when normal keratinocytes were cultured with nontumour-originated fibroblasts.
  
  
  CONCLUSIONS
  These observations indicate that BCCFs may differ from normal fibroblasts and may play a regulatory role in BCC biology.
authors.affiliation: Institute of Anatomy and Department of Dermatovenerology, First Faculty of Medicine; and Centre of Cell Therapy and Tissue Repair, Second Faculty of Medicine; Charles University, Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Lacina
authors.forename: K
authors.initials: K
authors.lastname: Smetana
authors.forename: B
authors.initials: B
authors.lastname: Dvoránková
authors.forename: R
authors.initials: R
authors.lastname: Pytlík
authors.forename: L
authors.initials: L
authors.lastname: Kideryová
authors.forename: L
authors.initials: L
authors.lastname: Kucerová
authors.forename: Z
authors.initials: Z
authors.lastname: Plzáková
authors.forename: J
authors.initials: J
authors.lastname: Stork
authors.forename: H-J
authors.initials: HJ
authors.lastname: Gabius
authors.forename: S
authors.initials: S
authors.lastname: André
mesh_terms: D000818:Animals; D002280:Basal Cell Carcinoma / Q000473:pathology*; D004847:Epithelial Cells; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D010641:Phenotype; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology*