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. Objectives: 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-Rag1null 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. © 2007 The Authors.