Endocrine Abstracts

Introduction: Ovarian cancer is the most lethal gynecological malignancy. Early diagnosis has a survival rate of 90%. Unfortunately, more than 70% of cases are diagnosed when the cancer has already metastasized, and survival rates do not exceed 30% in these cases. The sodium iodide symporter (NIS) is an integral plasma membrane glycoprotein expressed in the basolateral surface of the thyroid gland, where it mediates active transport of iodide. Radioiodide therapy (RAI) through NIS is the most effective therapy in thyroid cancer. Our group has demonstrated that NIS is expressed in ovarian surface epithelium and is overexpressed in human epithelial ovarian cancer, establishing NIS as a tumor marker. The aim of this study is to determine whether endogenous expression of NIS in ovarian cancer can be used as therapeutic tool usingRAI in ovarian tumors.

Materials and methods: serous ovarian cancer cell line (SKOV3) was transfected permanently with exogenous NIS (SKOV3-hNIS) and in vitro characterized by different techniques (western-blot, PCR, flow cytometry, immunofluorescence, iodide uptake). In vivo, NIS-transfected and not transfected cells were injected into flanks of nude and NSGs mice. NIStumor expression was analyzed by different techniques and NIS functionality in animal models was measured by SPECT-CT.¹³¹I treatment was tested in subcutaneous nude female mice. Human ovarian tumors samples received from the Mostoles Hospital were disaggregated and used to produce primary cultures and PDX animals.

Results: PCR and western-blot show NIS expression in both in vitro (cancer cells) and in vivo (xenotransplanted cells in animal models and human samples). Immunofluorescence and immunohistochemistry show that NIS expression occurs in plasma membrane. In vitro and in vivo (SPECT-CT) Iodide uptake assays show that the expression of NIS in plasma membrane is functional. ¹³¹I treatment in subcutaneous tumors show an overall decrease in tumor size of 71% vs a 632% increase in not treated tumors. We observed that more than 37% of tumors disappear in 25 days with just a single ¹³¹I dose.

Conclusion: NIS expression in human ovarian cancer cell lines is functional in vitro and in vivo, targeted to the plasma membrane, and able to accumulate iodide. A single dose of ¹³¹I reduces ovarian tumor growth in NIS-expressing tumors and is more effective than conventionally chemotherapy. Patient tumors are expressing NIS in the plasma membrane, which leads us to propose NIS as a therapeutic approach to the treatment of ovarian cancer through radio iodine.