Effect of host immunity on metastatic potential in renal cell carcinoma: the assessment of optimal in vivo models to study metastatic behavior of renal cancer cells.

There has been little information about metastatic behavior of renal cell carcinoma (RCC) cells because human cancers metastasize only rarely in immunodeficient mice. Moreover, it is difficult to know the effect of host immunity on RCC metastasis due to lack of such RCC cells as transplantable in not only xenograft models but also counterparts with intact immunity. Therefore, we scrutinized in vivo metastasis of RCC cells to seek for the optimal preclinical model to study metastatic behavior. The luciferase-expressing three representative human RCC cell lines (Caki-1, A498, and 786-O) and rat ACI-RCC cell which were established in our laboratory were transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice or immunocompetent ACI rats by intracardiac injection as well as orthotopic inoculation. Metastasis was monitored using a bioluminescent imaging technique. Metastasis was rare in the three human RCC cells even when they were directly disseminated into systemic circulation under the condition least susceptible to host immune attack in NOD/SCID mice. In contrast, ACI-RCC cells spontaneously metastasized to pulmonary tissue from orthotopic tumor sites and systemically spread via intracardiac route. Metastases were more extensive when the cells were inoculated into an immunodeficient host, implying suppressive effect of host immunity on colonization of RCC cells. These results suggest that the representative human RCC cells are not adequate resource to study metastasis but that the luciferase-labeled ACI-RCC cell characterized by its luminescent stability, enhanced tumorigenicity, and widespread metastatic potential provides a useful in vivo model for preclinical assessment of cancer progression and potential therapies against RCC.