In vivo expression and function of the sodium iodide symporter following gene transfer in the MATLyLu rat model of metastatic prostate cancer.
BACKGROUND
The sodium iodide symporter (NIS) mediates iodide uptake in thyroid follicular cells and provides a mechanism for effective radioiodide treatment of residual, recurrent, and metastatic thyroid cancers. This study investigated the clinical applications of NIS gene transfer for prostate cancer using the MATLyLu metastatic rat model.


METHODS
MATLyLu cells expressing NIS were injected subcutaneously in Copenhagen rats, which developed metastases in lymph nodes and lungs. NIS protein expression was evaluated by Western blot and immunohistochemistry, and function was measured by tissue gamma counts and whole-body imaging following radionuclide administration.


RESULTS
In vitro radioiodide-concentrating activity was increased up to 72-fold in a mixed population of MATLyLu-hNIS cells. NIS protein expression was confirmed in subcutaneous MATLyLu-hNIS tumors by immunohistochemistry and Western blot. Gamma counts of subcutaneous MATLyLu-hNIS tumors were 23-fold higher than parental MATLyLu tumors and radionuclide uptake in subcutaneous MATLyLu-hNIS tumors and lymph node metastases was visualized by whole-body image analysis.


CONCLUSIONS
NIS expression by a proportion of cells in a population was sufficient to confer radionuclide-concentrating function in subcutaneous and metastatic MATLyLu tumors. Ablation of residual normal and neoplastic prostate tissues by radioiodide after prostate-restricted NIS gene transfer might be a novel adjuvant therapy to prostatectomy for the treatment of advanced prostate cancer.
La Perle
Krista M D
KM
Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA.
Shen
Daniel
D
Buckwalter
Tara L F
TL
Williams
Bonnie
B
Haynam
Aaron
A
Hinkle
George
G
Pozderac
Rodney
R
Capen
Charles C
CC
Jhiang
Sissy M
SM
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D007279:Injections, Subcutaneous; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging*; D008297:Male; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D011877:Radionuclide Imaging; D018714:Radiotherapy, Adjuvant; D051381:Rats; D027981:Symporters / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters