In vivo expression and function of the sodium iodide symporter following gene transfer in the MATLyLu rat model of metastatic prostate cancer
| Autor: | Krista M. D. La Perle, Tara L.F. Buckwalter, Charles C. Capen, Aaron Haynam, Bonnie Williams, Sissy M. Jhiang, Daniel Shen, George H. Hinkle, Rodney V. Pozderac |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Sodium-iodide symporter Pathology medicine.medical_specialty Lung Neoplasms Injections Subcutaneous Urology Population Metastasis Iodine Radioisotopes Prostate cancer Prostate Tumor Cells Cultured medicine Animals Neoplasm Metastasis Radionuclide Imaging education Lymph node health care economics and organizations education.field_of_study Symporters business.industry Gene Transfer Techniques Prostatic Neoplasms Neoplasms Experimental medicine.disease Rats Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Lymphatic Metastasis Adenocarcinoma Immunohistochemistry Radiotherapy Adjuvant business |
| Zdroj: | The Prostate. 50:170-178 |
| ISSN: | 1097-0045 0270-4137 |
| DOI: | 10.1002/pros.10046 |
| Popis: | 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. Prostate 50: 170–178, 2002. © 2002 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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