Identification and metastatic potential of tumor-initiating cells in malignant rhabdoid tumor of the kidney.

PURPOSE Malignant rhabdoid tumor of the kidney (MRTK) is a rare and highly aggressive malignancy of infanthood. In an effort to delineate MRTK progression, we investigated the metastatic fate of some MRTK cells using xenotransplantation animal models and the tumor-initiating potential of CD133(+) MRTK cells. EXPERIMENTAL DESIGN We established two MRTK cell lines (JMU-RTK-1 and JMU-RTK-2) from patients with MRTK. We generated five luciferase-expressing MRTK cells for in vivo luminescent imaging and evaluated the metastatic fate in an orthotopic xenotransplantation model. Capacities of MRTK-initiating cells were examined in nonobese diabetic/severe combined immunodeficient mice after antibody-mediated magnetic bead sorting. Use of chemokine receptor CXCR4 expression as a metastatic marker was evaluated by flow cytometry and Western blotting. RESULTS MRTK cell lines showed distant organ metastasis. JMU-RTK-1, JMU-RTK-2, and G401 cells showed considerable aggressiveness compared with SWT-1 and SWT-2 cells (P < 0.05). Moreover, as few as 1,000 CD133(+) MRTK cells initiated tumor development in nonobese diabetic/severe combined immunodeficient mice by 21 days (60-100%) in all examined cell lines, although the same number of CD133(-) MRTK cells could not form tumors (0%). Interestingly, the metastatic potential of the CD133(+) population remained unaffected compared with a nonenriched population. The potential metastatic marker CXCR4 was expressed in CD133(+) and CD133(-) MRTK cells, and CD133(-) cells seemed to play a cooperative role in terms of tumorigenicity and metastasis. CONCLUSIONS These results suggest that CD133(+) cells may determine the metastatic fate of MRTK cells and that CD133(-) cells may play an auxiliary role in tumor progression and metastasis.