Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Introduction: Previous in vivo studies demonstrated that hypoxia measured by pimonidazole staining is associated with local tumor control in human head and neck squamous cell carcinoma (hHNSCC). This project intends to identify and validate genes which are expressed differently in hypoxic and oxic cells and therefore may play an important role in radiation resistance. This might lead to the establishment of new targets and biomarkers for potential therapeutic. Materials and methods: Seven different hHNSCC in nude mice were studied. For gene expression analysis untreated tumors were excised and stained for pimonidazole hypoxic areas. Using laser-capture microdissection (LCM), material was collected separately from consecutive unstained slides. RNA was isolated and subjected to gene expression analysis using nanoString technologies. The applied gene panel included hypoxia classifier (Toustrup et al.) as well as genes that have been reported to be involved in radioresistance, such as genes which are encoding for putative cancer stem cell markers. Results: Several genes showed large differences in expression between hypoxic and well perfused areas. Differences were found in the expression level of hypoxia-associated genes within the hypoxic areas between the individual tumor models. In addition, the more radioresistant tumors do not necessarily coincide with the intensity of the expression of these genes. Besides the hypoxic gene signature, genes encoding for stem cell markers, are significantly different between these two micromilieu areas. Conclusion: LCM allows analysing RNA from different microenvironmental areas. We found significantly different expressions of genes which can play an important role with regard to radioresistance in tumors, and are involved in processes, such as DNA repair, proliferation and invasiveness. In this way, new targets and biomarkers could be established in order to obtain potential therapeutic approaches in combination with radiotherapy.