CEINGE-Advanced Biotechnology, Naples, Italy.
Cancer. 2013 Feb 15;119(4):729-38. doi: 10.1002/cncr.27794. Epub 2012 Oct 1.
Despite the well recognized expression of the cell surface markers cluster of differentiation 44 (homing cell adhesion molecule) and CD133 (Prominin 1) on human colorectal cancer stem cells (CCSCs), these molecules do not appear to be effective targets for stem cell-directed therapies. Because the surface marker CD66c (also known as carcinoembryonic antigen-related cell adhesion molecule 6) has demonstrated promise as a therapeutic target in pancreatic malignancy, the authors evaluated its potential as a target for stem cell-directed treatment of colorectal cancer.
First, the authors characterized CD66c expression by flow cytometry and immunohistochemistry in colon cancer samples and in normal colon tissues. Then, the coexpression of CD66c and CD133 was evaluated on putative CCSCs. CD66c expression also was measured in stem cell-enriched colon spheres. Finally, the effects of small-interfering RNA-mediated CD66c silencing on the in vitro and in vivo growth of Caco2 colon cancer cells were evaluated.
CD66c expression was significantly higher in colon cancers than in contiguous normal colon tissues and paralleled cancer stage. CD66c was absent in CD133-positive cells that were isolated from normal colon, whereas its expression was brightest (CD66c(bright) ) in CD133-positive cells from colon cancer samples. In vitro experiments demonstrated that colon spheres were considerably enriched in a CD66c(bright) population in a fashion comparable to the enrichment observed in fresh liver metastases. In vitro proliferation and clonogenic potential were hampered when CD66c was silenced in Caco2 cells. Finally, in vivo xenograft experiments demonstrated that CD66c silencing almost completely abrogated the tumorigenic potential of Caco2 cells.
CD66c(bright) expression was associated with colon cancer stem cells and CD66c silencing blocked tumor growth, thereby opening the way to a potential new treatment for colon cancer.
尽管人类结直肠癌干细胞（CCSCs）表面标志物分化簇 44（归巢细胞黏附分子）和 CD133（Prominin 1）的表达得到了充分的认识，但这些分子似乎并不是针对干细胞定向治疗的有效靶点。由于表面标志物 CD66c（也称为癌胚抗原相关细胞黏附分子 6）在胰腺恶性肿瘤中作为治疗靶点显示出了一定的前景，作者评估了其作为结直肠癌干细胞定向治疗靶点的潜力。
首先，作者通过流式细胞术和免疫组织化学方法对结肠癌样本和正常结肠组织中的 CD66c 表达进行了特征描述。然后，评估了 CD66c 和 CD133 在假定的 CCSCs 上的共表达。还测量了富含干细胞的结肠球体中的 CD66c 表达。最后，评估了小干扰 RNA 介导的 CD66c 沉默对 Caco2 结肠癌细胞体外和体内生长的影响。
CD66c 的表达在结肠癌中明显高于相邻的正常结肠组织，并且与癌症分期相平行。CD133 阳性细胞从正常结肠中分离出来时，CD66c 缺失，而从结肠癌样本中分离出来的 CD133 阳性细胞表达最亮（CD66c（bright））。体外实验表明，结肠球体在 CD66c（bright）群体中明显富集，这种富集方式与在新鲜肝转移中观察到的富集方式相当。当 Caco2 细胞中的 CD66c 被沉默时，体外增殖和克隆形成能力受到阻碍。最后，体内异种移植实验表明，CD66c 沉默几乎完全阻断了 Caco2 细胞的致瘤潜力。
CD66c（bright）表达与结肠癌症干细胞相关，CD66c 沉默阻断了肿瘤生长，从而为结肠癌的潜在新治疗方法开辟了道路。
