Meng Qinghui, Wu Weihua, Pei Tiemin, Li Long, Tang Xiaolong, Sun Haobo
Department of General Surgery, The First Clinical Medical School of Harbin Medical University Harbin 150001, China.
Department of Endocrinology, The First Clinical Medical School of Harbin Medical University Harbin 150001, China.
Am J Transl Res. 2016 Oct 15;8(10):4233-4241. eCollection 2016.
Some colorectal carcinoma (CRC) invades into vessels and has distal metastasis, largely attributable to the dissemination of tumor cells into circulation as circulating tumor cells (CTCs). Moreover, cancer stem cells (CSCs) within CTCs, which are termed as circulating tumor stem-like cells (CTSCs), are critical for formation of distal metastatic tumors. Although different cell surface markers have been used to characterize and isolate CTCs or CSCs in CRC, no good marker has been identified so far for CTSCs. Here, we show evidence that CD262+ CRC cells appeared to be highly enriched for CTSCs in CRC. CD262+ CRC cells formed more tumor spheres in culture, exhibited higher chemo-resistance, had higher ratio of developing tumors after serial adoptive transplantation in nude mice, and had higher frequency of developing distal metastatic tumor, compared to traditional CD133+ or CD44+ CRC cells. Moreover, tumor cells were significantly more frequently detected in the circulation when CD262+ CRC cells were subcutaneously transplanted. Finally, we detected high CD262 levels in the stage IV CRC specimens, which were associated with poor prognosis of the patients. Together, these data suggest CD262+ may be a novel CTSC markers and selective elimination of CD262+ CRC cells may substantially improve the current CRC therapy.
一些结直肠癌（CRC）会侵犯血管并发生远处转移，这很大程度上归因于肿瘤细胞以循环肿瘤细胞（CTC）的形式进入血液循环。此外，CTC中的癌症干细胞（CSC），即循环肿瘤干细胞样细胞（CTSC），对于远处转移性肿瘤的形成至关重要。尽管已使用不同的细胞表面标志物来表征和分离CRC中的CTC或CSC，但迄今为止尚未鉴定出用于CTSC的良好标志物。在此，我们证明有证据表明CD262 + CRC细胞似乎在CRC中高度富集CTSC。与传统的CD133 +或CD44 + CRC细胞相比，CD262 + CRC细胞在培养中形成更多的肿瘤球，表现出更高的化疗抗性，在裸鼠中进行系列过继移植后形成肿瘤的比例更高，并且发生远处转移性肿瘤的频率更高。此外，当皮下移植CD262 + CRC细胞时，在循环中检测到肿瘤细胞的频率明显更高。最后，我们在IV期CRC标本中检测到高CD262水平，这与患者的不良预后相关。总之，这些数据表明CD262 +可能是一种新型的CTSC标志物，选择性消除CD262 + CRC细胞可能会显著改善当前的CRC治疗。
