Prognostic impact of CD133 expression as a tumor-initiating cell marker in endometrial cancer.
Tumor-initiating cells are known to be the major source of tumor propagation and might be an attractive therapeutic target. The present study dissected the roles of CD133 as a tumor-initiating cell marker in endometrial cancer and investigated the prognostic impact of this marker expression. Flow cytometry using 6 endometrial cancer cell lines revealed that the frequency of CD133(+) cells varied widely among the cell types and that Ishikawa and MFE280 cells contained significantly higher ratio (10%-20%) of such cells; therefore, these were subjected to the subsequent analyses. Sorted CD133(+) cells showed more aggressive proliferative potential in vitro and more increased tumorigenicity in nude or NOD/SCID mice than CD133(-) cells and generated both CD133(+) and CD133(-) cells. Furthermore, they showed apparent resistance to cisplatin- or paclitaxel-induced cytotoxicity compared with CD133(-) cells. CD133(+) cells had a greater S-phase fraction than CD133(-) cells, and the serum starvation that induced G0/G1 accumulation decreased the population of CD133(+) cells. Finally, we immunohistochemically analyzed the CD133 expression in endometrial cancer specimens from 62 patients. CD133 expression was not significantly associated with any of the clinicopathologic characteristic of tumors. However, the Kaplan-Meier analysis revealed that tumors with high CD133 expression showed worse overall survival (P = .023, log-rank test) than those with low CD133 expression; and the Cox regression hazard model found that high CD133 expression was an independent prognostic factor (P = .045). Thus, the present study demonstrates that CD133 is not only a tumor-initiating cell marker but also a critical prognostic marker in endometrial cancer.
Nakamura
Mitsuhiro
M
Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
Kyo
Satoru
S
Zhang
Bo
B
Zhang
Xiuzhi
X
Mizumoto
Yasunari
Y
Takakura
Masahiro
M
Maida
Yoshiko
Y
Mori
Noriko
N
Hashimoto
Manabu
M
Ohno
Satoshi
S
Inoue
Masaki
M
D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007564:Japan / Q000453:epidemiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D011379:Prognosis; D053262:Receptors, OX40 / Q000378:metabolism*; D015996:Survival Rate; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human