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


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.
Yoshimura
Ichiro
I
Department of Urology, National Defense Medical College, Tokorozawa, Japan. ichiro_y4740@yahoo.co.jp
Mizuguchi
Yasunori
Y
Miyajima
Akira
A
Asano
Tomohiko
T
Tadakuma
Takushi
T
Hayakawa
Masamichi
M
D000256:Adenoviridae; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000517:prevention & control* / Q000556:secondary*; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
D040281:Vascular Endothelial Growth Factor Receptor-1