Suppression of lung metastasis of renal cell carcinoma by the intramuscular gene transfer of a soluble form of vascular endothelial growth factor receptor I

Purpose: We clarified whether adenovirus mediated intramuscular gene transfer of soluble vascular endothelial growth factor receptor 1 (sFlt-1) can inhibit lung metastasis of renal cell carcinoma. Materials and Methods: We constructed the adenovirus vector AdsFlt-1, which expresses soluble Flt-1 protein. Functional validation of the vector was determined by HUVEC (in vitro human umbilical vein endothelial cell) proliferation inhibition assay. The efficacy of AdsFlt-1 was tested in a Renca murine renal cell carcinoma lung metastasis model. BALB/c mice were injected with Renca cells, followed by the intramuscular administration of AdsFlt-1 24 hours later. Lung specimens were harvested 17 days later and the number of lung metastases was counted. Immunohistochemical analysis of the specimen for angiogenesis and apoptosis was done. Results: Treatment with adenovirus expressed sFlt-1 inhibited HUVEC proliferation. The intramuscular administration of AdsFlt-1 significantly inhibited lung metastasis of Renca cells. Immunohistochemical analysis of the lung specimen showed fewer neovessel formations and more apoptotic cells in AdsFlt-1 treated tumors in mice. Conclusions: The intramuscular administration of AdsFlt-1 effectively inhibited lung metastasis in a murine model of renal cell carcinoma. Because of the simplicity of this therapy, it may well be useful as an effective adjuvant therapy for renal cell carcinoma.