Different status of extracellular components associated with cellular radioresistance

Radioresistance varies significantly in human tumor cells, thereby impacting the efficacy of radiotherapy. The pursuit of the idea that gene expression profiles could be used to identify radioresistant cell lines from others formed the basis of this study. Global gene expression profiles of 15 human tumor and normal fibroblast cell lines were analyzed using DNA microarrays. To begin, 6 of the cell lines were categorized into radioresistant (RG) or non-resistant (NRG) groups according to the radiation dose required to reduce their survival to 10% (D10). Genes whose expression was specific to each group at 1 or 3 hr after irradiation were isolated by ANOVA and a two-dimensional hierarchical clustering method. Then, the remaining 9 cell lines were subjected to k-nearest neighbor pattern classification. Classifying the 9 test-cell lines reasonably related to the cellular D10 value was effective for a set of 46 genes at 1 hour and for another set of 44 genes at 3 hours after irradiation, respectively. Of these genes, 25 showed altered expression at both time points in the NRG or RG, but independently were unable to classify the test cell lines. In general, genes that inhibited apoptosis and promoted proliferation were upregulated in the RG, while pro-apoptotic genes tend to be activated in the NRG. Interestingly, genes that localized in extracellular matrix were downregulated in the RG. Different status of the extracellular microenvironment may be a cause of different mobility of tumor cells following invasive or metastatic activity. These results suggest that certain gene categories may be useful not only for predicting the radioresistance of human tumor cells but also for gaining a better understanding of the relationship between tumorigenesis and radioresistance. In conclusions, radioresistant cell lines analyzed in this study showed certain radiation-induced changes in gene expression profiles that are different from the profile changes of the more-sensitive cell lines.10th Anniversary of Kazusa Arc International Symposium on Advanced Functional Genomic