Abstract
Abstract Introduction: Nodular melanoma is one of the most life threatening tumors with frequently poor therapeutic outcome. Similarly to other the tumors, the intercellular interactions may be of crucial importance for biological properties of melanoma and course of the disease. This study is mapping the effect of melanoma cells and melanoma associated fibroblasts on keratinocytes as compared with effect of neural crest stem cells. Methods: 100 samples removed during radical melanoma resection were analyzed by histology and 20 of them by immunohistochemistry and compared with in vitro models. For in vitro models of intercellular interactions we co-cultured in transwell systems melanoma cells or neonatal melanocytes or neural crest stem cells respectively with human normal keratinocytes. Further, we employed also melanoma associated fibroblasts and normal human dermal fibroblasts respectively in above mentioned culture system. Transcriptional analysis of these models was carried out in collaboration with the Institute of Molecular Genetics of the ASCR on the whole genome level by using Illumina microarrays. Results: In tissue surrounding nodular melanoma we have observed significant hyperplasia of epithelial layer with aberrant suprabasal expression of keratin 14 (K14) along with absence of K10 - marker of differentiated epidermal keratinocytes. In vitro models revealed that melanoma cells, neural crest stem cells and also melanoma associated fibroblasts were able to influence expression of K14, but also expression of K19 and K8 as well as of vimentin in cocultured keratinocytes. Cytokines and growth factors such as FGF2, CXCL1, IL8 and VEGFA seem to participate in this activity of melanoma cell to keratinocytes. Conclusion: Melanoma cells as well as melanoma associated fibroblasts are able to modify the landscape of tissue surrounding the proliferating malignant clone. These interactions result in maintenance of low differentiation status of keratinocytes in vivo as well as in vitro. This interaction further highlights the role of intercellular interactions in melanoma, but the functional significance for melanoma biology requires further analysis. This study was supported by the Charles University project PRVOUK 27-1 and by the Grant Agency of the Czech Republic project no 304/121/333. Citation Format: Ondrej Kodet, Lukas Lacina, Barbora Dvorankova, Michal Kolar, Hynek Strnad, Karel Smetana, Jr.. Melanoma cells induce stem cells like fenotype of normal human keratinocytes. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B26.
Published Version
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