Abstract
Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.
Highlights
Anaplastic thyroid cancer (ATC) is rare and represents less than 2% of all thyroid cancer [1]
To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy
Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in Anaplastic thyroid carcinoma (ATC) cells
Summary
Anaplastic thyroid cancer (ATC) is rare and represents less than 2% of all thyroid cancer [1]. ATC does not concentrate iodide due to the loss of expression of sodium iodide symporter (NIS) gene. NIS is a membrane protein with 13 putative transmembrane domain [4]. This symporter is driven by low internal sodium concentration and symports 2 sodium ions for every iodide ion into cells. Function of iodide transport of NIS has been used in radioiodide imaging and therapy. By introducing NIS gene into variety of cancer cells which do not concentrate iodide, it showed a promising therapeutic effect after administrating therapeutic isotopes [7]. We have shown the effectiveness of NIS-mediated radioiodide therapy on tumors derived from ATC cell line, ARO [8]. The model in previous study was stable cells established by transient transfection and clonal expansion
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