TY - JOUR
T1 - In vivo growth of transitional and renal cell carcinoma cell lines can be suppressed by the adenovirus-mediated expression of a soluble form of vascular endothelial growth factor receptor
AU - Ichikura, Haruhiko
AU - Eto, Masatoshi
AU - Ueno, Hikaru
AU - Harada, Mamoru
AU - Takayama, Koichi
AU - Tokuda, Noriaki
AU - Tatsugami, Katsunor
AU - Naito, Seiji
PY - 2006/5
Y1 - 2006/5
N2 - Antiangiogenic therapy is a promising strategy for the treatment of cancer since tumor development and metastases require angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most important factors in tumor angiogenesis. In the present study, we investigated the antitumor effect of an adenovirus (AdVEGF-ExR) expressing the extracellular domain of the human VEGF receptor (flt-1) using two different urological tumor/mouse systems. RENCA, a renal cell carcinoma of BALB/c origin, and MBT-2, a poorly differentiated transitional carcinoma of C3H/He origin, were used. Both types of tumor were in vitro infected with AdVEGF-ExR and inoculated subcutaneously into the abdomens of syngenenic mice, and tumor growth was measured twice weekly. In some experiments, BALB/c mice with established RENCA tumors were injected intramuscularly with AdVEGF-ExR as a therapeutic model. The cytotoxicity of spleen cells from the tumor-rejected mice was assessed by 51Cr-release assay. Although the in vitro cell growth of either MBT-2 or RENCA was not affected by infection with AdVEGF-ExR, the in vivo growth of both AdVEGF-ExR-infected tumors was significantly suppressed in the syngeneic mice. In addition, although 2 of 5 mice rejected the AdVEGF-ExR-infected RENCA, tumor-specific cytotoxic T lymphocytes were not generated from their spleen cells, thus suggesting no cellular immune response. In a therapeutic model, intramuscular injections of AdVEGF-ExR at a remote site also significantly suppressed the growth of the subcutaneously established RENCA. These results indicate that the adenovirus-mediated expression of a soluble VEGF receptor can be an effective therapy for urological cancer treatment; however, such VEGF-targeted gene therapy is not necessarily accompanied by subsequent antitumor T cell immunity.
AB - Antiangiogenic therapy is a promising strategy for the treatment of cancer since tumor development and metastases require angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most important factors in tumor angiogenesis. In the present study, we investigated the antitumor effect of an adenovirus (AdVEGF-ExR) expressing the extracellular domain of the human VEGF receptor (flt-1) using two different urological tumor/mouse systems. RENCA, a renal cell carcinoma of BALB/c origin, and MBT-2, a poorly differentiated transitional carcinoma of C3H/He origin, were used. Both types of tumor were in vitro infected with AdVEGF-ExR and inoculated subcutaneously into the abdomens of syngenenic mice, and tumor growth was measured twice weekly. In some experiments, BALB/c mice with established RENCA tumors were injected intramuscularly with AdVEGF-ExR as a therapeutic model. The cytotoxicity of spleen cells from the tumor-rejected mice was assessed by 51Cr-release assay. Although the in vitro cell growth of either MBT-2 or RENCA was not affected by infection with AdVEGF-ExR, the in vivo growth of both AdVEGF-ExR-infected tumors was significantly suppressed in the syngeneic mice. In addition, although 2 of 5 mice rejected the AdVEGF-ExR-infected RENCA, tumor-specific cytotoxic T lymphocytes were not generated from their spleen cells, thus suggesting no cellular immune response. In a therapeutic model, intramuscular injections of AdVEGF-ExR at a remote site also significantly suppressed the growth of the subcutaneously established RENCA. These results indicate that the adenovirus-mediated expression of a soluble VEGF receptor can be an effective therapy for urological cancer treatment; however, such VEGF-targeted gene therapy is not necessarily accompanied by subsequent antitumor T cell immunity.
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U2 - 10.3892/or.15.5.1333
DO - 10.3892/or.15.5.1333
M3 - Article
C2 - 16596207
AN - SCOPUS:33744977255
VL - 15
SP - 1333
EP - 1337
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 5
ER -