Epstein-Barr virus induces morphological and molecular changes in thyroid neoplastic cells.

Abstract

Although the evolution of differentiated thyroid cancer (DTC) is usually indolent, some tumors grow fast, metastasize, and may be fatal. Viruses have been associated with many human tumors, especially the Epstein-Barr virus (EBV), which shows a high viral load in DTC. In order to evaluate the ability of the virus to cause morphological and molecular changes in neoplastic thyroid cell lines TPC-1, BCPAP, and 8505C, a viral adaptation was performed for the analysis of EBV cytopathic effect (CPE), viral kinetics and gene expression analysis of oncogenes KRAS, NRAS, HRAS, and TP53. Comparison of inoculated cells with non-inoculated control cells showed that all tumor cell lines were permissive to the virus. The virus caused CPE in the TPC-1 and 8505C, but not in BCPAP cells. Viral kinetic was similar in both BCPAP and 8505C with a point of eclipse at 24 h post infection. TPC-1 cell line displayed a decreasing growth curve, with highest viral load right after inoculation, which decreased over time. There was hyperexpression of TP53 and NRAS in BCPAP cell (p = 0.012 and p = 0.0344, respectively). The 8505C cell line presented NRAS hyperexpression (p = 0.0255), but lower TP53 expression (p = 0.0274). We concluded that neoplastic thyroid cell lines are permissive to EBV that the virus presents different viral kinetic patterns in different cell lines and produces a CPE on both well-differentiated and undifferentiated thyroid cell lines. We also demonstrated that EBV interferes in oncogene expression in thyroid neoplastic cell lines, suggesting that these effects could be related to different tumor progression patterns.