Epithelial‐mesenchymal cross talk in cancer behavior (1047.1)

Abstract

Epithelial‐mesenchymal interaction is important in the morphogenesis, development, wound healing and also in cancer behavior. It is dependent on the range of cytokines, chemokines, growth, proliferating and transforming factors produced by both the counterpartners. Tumor stroma contains, except the mesenchyme, also blood vessels, and the inflammatory cells. We focused our research on most abundant cell component of cancer stroma on cancer‐associated fibroblasts (CAF). They are producers of extracellular components, which are necessary to formation bioactive cancer microenvironment and are able to influence the biology of tumor predominantly the differentiation status of tumor cells and their migratory potential. We have isolated CAF from malignant tumors (squamous cell carcinoma, basal cell carcinoma (BCCF), melanoma, and skin metastasis of breast cancer) and have shown that these CAF are able to influence the differentiation status of co‐cultured cells from normal squamous or breast cancer epithelium. The results were compared with control experiments using normal human dermal fibroblasts, 3T3 mouse fibroblasts, and 3T3 fibroblasts influenced by the fibroblasts prepared from the basal cell carcinoma. Our results demonstrated that expression of luminal marker keratin 8 was influenced only by CAFs prepared from any tested tumors. In contrast, all tested types of fibroblasts showed a strong stimulatory effect on the expression of basal/myoepithelial marker keratin 14. Since keratin 14 is a marker of basal myoepithelial cells and keratin 8 is a marker of luminal cells, these double‐positive cells can be considered for precursor cells with properties close to stem cells. Their presence in clinical samples indeed signals very poor prognosis in cancer‐suffering patiens. In conclusion, our data indicate that CAFs are able to influence the phenotype of a breast cancer cell line and this effect is based on a tumor type‐unspecific mechanism.