Evaluation of head and neck squamous cell carcinoma invasiveness by the electrical resistance breakdown assay

Abstract

Invasion of tumor cells into the surrounding tissue is a hallmark of cancer. Squamous cell carcinomas of the head and neck region (HNSCC) are characterized by their early primarily lymphatic metastatic spread. The aim of the present study was to evaluate the use of the electrical resistance breakdown assay for determining HNSCC tumor cell invasiveness. The assay utilizes the high transepithelial electrical resistance (TEER) of an epithelial MDCK-C7 monolayer as a sensitive indicator of monolayer integrity and permeability. MDCK-C7 cells were grown to confluence in microfilter membrane cups. 3 x 10(6) cancer cells of cell lines UM-SCC-3, UM-SCC-27, UMB-SCC-745, UMB-SCC-864, UMB-SCC-969 and UT-SCC-26A derived from HNSCC tumors, were seeded on top of this epithelial test barrier. A7-melanoma cells served as a positive control whereas MDCK-C7 cells were used as a negative control and were applied in the same number as the tested tumor cells. TEER was measured over the following days and compared to control values. A significant reduction in TEER was observed in the UMB-SCC-745, UMB-SCC-969 and UT-SCC-26A cell lines within the first 72 h, whereas no significant reduction in TEER was seen in the UM-SCC-3, UM-SCC-27 and UMB-SCC-864 cell lines. HNSCC cell lines in general are found to be less invasive in the resistance breakdown assay compared to other tumor cells such as A7-melanoma cells, however, the electrical resistance breakdown assay appears capable of demonstrating differences in invasiveness between different HNSCC cell lines and therefore potentially could serve as a versatile tool in distinguishing high and low invasive tumors with a potential application as a diagnostic and prognostic marker in clinical investigations.