Clinical significance of radiation-induced CD133 expression in residual rectal cancer cells after chemoradiotherapy - PubMed (original) (raw)

doi: 10.3892/etm.2011.438. Epub 2011 Dec 28.

Koji Tanaka, Susumu Saigusa, Yuji Toiyama, Yuhki Morimoto, Hiroyuki Fujikawa, Takashi Iwata, Kohei Matsushita, Takeshi Yokoe, Hiromi Yasuda, Yasuhiro Inoue, Chikao Miki, Masato Kusunoki

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Clinical significance of radiation-induced CD133 expression in residual rectal cancer cells after chemoradiotherapy

Aya Kawamoto et al. Exp Ther Med. 2012 Mar.

Abstract

CD133 and CD44 have been considered as markers for colorectal cancer stem cells (CSCs). The association of CD133 and CD44 expression with radiation has not been fully examined in rectal cancer. Both CD133 (PROM) and CD44 mRNA levels were measured in post-chemoradiotherapy (CRT) specimens of 52 rectal cancer patients using real-time RT-PCR and compared to clinicopathological variables and clinical outcome. Their protein levels were examined in the radiation-treated HT29 human colon cancer cell line. Post-CRT CD133 in residual cancer cells was significantly higher than matched pre-CRT CD133 in biopsy specimens (n=30). By contrast, CD44 was significantly lower in post-CRT specimens (P<0.01). CD133 was associated with distant recurrence after CRT followed by surgery (P<0.05). Patients with elevated CD133 in residual cancer cells showed poor disease-free survival (P<0.05). No significant association between post-CRT CD44 and clinical outcome was found. The in vitro study showed that CD133 protein was increased in a radiation dose-dependent manner, despite of the decreased number of clonogenic radiation-surviving cells. CD44 protein was decreased after irradiation. CD133, but not CD44, was increased in radiation-resistant surviving colon cancer cells. Post-CRT CD133 in residual cancer cells may predict metachronous distant recurrence and poor survival of rectal cancer patients after CRT.

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Figures

Figure 1.

Figure 1.

Survival according to post-CRT CD133 or CD44 expression. Patients with post-CRT CD133 above the cutoff value (High) showed significantly worse disease-free survival (log-rank test; P=0.0229).

Figure 2.

Figure 2.

CD133 and CD44 expression in paired pre- and post-CRT specimens. CD133 was higher in post-CRT specimens than that in the pre-CRT specimens (P=0.01). By contrast, CD44 was lower in the post-CRT residual cancer cells than in the pre-CRT biopsy specimens (P<0.001). Data are presented as the means ± standard error.

Figure 3.

Figure 3.

(A) Clonogenic survival assay of radiation-treated HT-29 cells. Clonogenic survival fractions of HT-29 cells were decreased in a radiation dose-dependent manner. Data are presented as the means ± standard deviation. Asterisk indicates statistically significant difference. (B and C) Expression of CD133 and CD44 in radiation-treated HT-29 cells. CD133 protein was increased in a radiation dose-dependent manner. By contrast, CD44 protein was decreased after irradiation.

Figure 4.

Figure 4.

Immunoreactive CD133 and CD44 expression in residual cancer cells. Immunoreactive CD133 protein was located in the cytoplasm and at an apical/ endoluminal surface of residual cancer cells (A: magnification, x200; C: magnification, x400). Immunoreactive CD44 protein was located at the surface membrane of residual cancer cells (B: magnification, x200; D: magnification, x400). No obvious concordance was found between CD133 and CD44 positivity of residual cancer cells.

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