Year: 2018
Type: conference-abstract
Abstract: Material and MethodsThe present study was designed to establish a panel of patient-derived HNSCC cell lines with individual subclones and to subject them to molecular characterization and functional analyses of radiosensitivity.Short tandem repeat (STR) typing was used for identification in comparison to previously preserved tumor material.Several markers, including pan-Cytokeratin, EpCAM, EGFR and fibroblast-specific protein were examined by immunofluorescence and flow cytometry.Clonogenic survival upon irradiation with single doses of 0-8 Gy and a fractionated regimen of 1 to 4x 2 Gy was analyzed.Molecular characterization was started with array comparative genomic hybridization (aCGH) assays in order to analyze DNA copy number changes. ResultsThe established primary cell cultures of so far 2 patients and their individual subclones (5 each) showed unique STR profiles and exhibit long-term proliferation capacity.Thus, they can be considered as novel and immortalized cell lines.We observed clear inter-and intra-individual differences in epithelial marker expression and in clonogenic survival upon different irradiation regimens suggesting that HNSCC inter-and intra-tumoral heterogeneity can be reflected by these cell culture models -at least to a certain extent.We found profound differences in aCGH profiles between the cell lines from different patients.Furthermore, we saw clear changes in DNA copy number alterations between intra-individual subclones.Conclusion To our knowledge, the present cell line panel is a so far unique platform to analyze tumor heterogeneity of HNSCC.We suggest that differences in the radiation response can be reflected by molecular data of several levels.To this end, we will continue the molecular characterization of the established cell lines on the methylome, mRNAome, and miRNAome level and will include more patients.Correlation analyses of functional data of the radiation response with molecular data will help to identify pathways and/or networks that are essentially involved in therapy resistance.
Source: Radiotherapy and Oncology
Authors: R. Kulshrestha, A.K. Rathi, S. Kapoor, K. Singh, S. Arora, S.K. Polipalli, A. Jindal
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,770
OpenAlex ID: W2808965692