DRUG SCREENING OF ORAL CARCINOMA CELL LINES USING PLASTIC, MOUSE OR HUMAN TUMOR DERIVED MATRICES

Objectives Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Traditionally, cancer cell lines cultured in 2D are used to predict the efficacy of new anti-cancer compounds. However, this method has low predicting value for efficacy since more than 80% of the cancer drugs, which have promising effect in pre-clinical studies, fail in Phase II clinical trials. Our group has developed human matrix based product, Myogel, which is extracted from leiomyoma tissue. Our hypothesis is that Myogel represents better the in vivo condition compared with the 2D plastic wells, or even wells coated with mouse derived Matrigel®. We selected 12 OSCC cell lines and 19 anti-cancer compounds, targeting mTOR and epidermal growth factor receptor (EGFR) signalling pathways. The High Throughput Drug Screening method with five different conditions were used: cells in 2D plastic wells; on top and within Matrigel® or Myogel. Additionally, the morphology of OSCC cells and EGRF location were studied using immunofluorescence staining and confocal microscope. Findings Cancer cells on top and within Myogel were less responsive to EGFR inhibitors compared to cells cultured in 2D plastic or Matrigel®. However, in case of mTOR inhibitors, similar efficacy of the drugs in all conditions was seen. The morphology of the carcinoma cells differed depending on the matrix. Within Matrigel, the cells formed isolated round-shaped organoids, whereas the cells within Myogel were stellate-shaped. Immunofluorescent staining revealed that in 2D and Matrigel, EGFR was located primarily on the cell membranes, while in Myogel, the staining was mainly in the cytoplasm. Conclusions Carcinoma cells showed different behaviours and responses to anti-cancer compounds depending on the testing conditions. Comparison between clinical data and our in vitroresults are still needed to reveal the most reliable condition for cancer drug testing.