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


METHODS
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.
Yanagisawa
Satohiko
S
Department of Pediatric Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Kadouchi
Ichiro
I
Yokomori
Kinji
K
Hirose
Masao
M
Hakozaki
Michiyuki
M
Hojo
Hiroshi
H
Maeda
Kosaku
K
Kobayashi
Eiji
E
Murakami
Takashi
T
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018335:Rhabdoid Tumor / Q000378:metabolism / Q000556:secondary*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D051598:Whole Body Imaging
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D008156:Luciferases