Kawamoto Aya, Tanaka Koji, Saigusa Susumu, Toiyama Yuji, Morimoto Yuhki, Fujikawa Hiroyuki, Iwata Takashi, Matsushita Kohei, Yokoe Takeshi, Yasuda Hiromi, Inoue Yasuhiro, Miki Chikao, Kusunoki Masato
Departments of Gastrointestinal and Pediatric Surgery and.
Exp Ther Med. 2012 Mar;3(3):403-409. doi: 10.3892/etm.2011.438. Epub 2011 Dec 28.
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.
CD133和CD44被认为是结直肠癌干细胞（CSCs）的标志物。CD133和CD44表达与放疗的关系在直肠癌中尚未得到充分研究。使用实时逆转录聚合酶链反应（RT-PCR）检测了52例直肠癌患者放化疗（CRT）后的标本中CD133（PROM）和CD44的mRNA水平，并与临床病理变量和临床结局进行了比较。在经放疗的HT29人结肠癌细胞系中检测了它们的蛋白水平。残留癌细胞中CRT后的CD133显著高于活检标本中配对的CRT前CD133（n=30）。相比之下，CRT后标本中的CD44显著降低（P<0.01）。CRT后行手术治疗，CD133与远处复发相关（P<0.05）。残留癌细胞中CD133升高的患者无病生存期较差（P<0.05）。未发现CRT后CD44与临床结局之间存在显著关联。体外研究表明，尽管克隆形成性放疗存活细胞数量减少，但CD133蛋白以辐射剂量依赖性方式增加。放疗后CD44蛋白减少。在耐辐射存活的结肠癌细胞中，CD133增加，而CD44未增加。残留癌细胞中CRT后的CD133可能预测直肠癌患者CRT后异时性远处复发和不良生存。
