Abstract
Since renal cell carcinoma is considered an immunogenic tumor, testing therapeutic strategies has been impeded by the lack of relevant tumor models in immunocompetent animals. Recent advances in bioluminescence imaging permit sensitive in vivo detection and quantification of cells emitting light. Thus, we established bioluminescent rat renal cell carcinoma cell lines for immunocompetent rats. The rat renal cell carcinoma cell line ACI-RCC stemming from chemically induced renal cell carcinoma in syngeneic ACI rats was stably transfected with a recombinant retroviral vector encoding luciferase genes derived from fireflies (ACI-RCC-ffLuc) or click beetles (ACI-RCC-cbLuc). Cell line growth patterns were characterized by bioluminescence imaging. Linear correlations noted observed between cell number and photon counts in each cell type. ACI-RCC-cbLuc emitted light about 500-fold higher than ACI-RCC-ffLuc. When transplanted subcutaneously, only ACI-RCC-ffLuc grew, possibly because of less antigenicity. ACI-RCC-ffLuc photon emission correlated significantly with subcutaneous tumor size. Orthotopic tumor growth and subsequent metastatic spread were monitored with time by increased photon intensity on bioluminescence imaging. Based on ACI-RCC-cbLuc bioluminescent intensity the in vitro screening test allowed the identification of several anticancer agents, including molecules related to human renal cell carcinoma progression. The new in vivo rat renal cell carcinoma model with luciferase labeled tumor cells allowed us to monitor tumor growth noninvasively and semiquantitatively by bioluminescence imaging. This model system coupled with in vitro screening permits precise evaluation of tumor behavior in intact animals and determination of the therapeutic efficacy of anticancer agents for renal cell carcinoma.
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