Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan.
PLoS One. 2013 Apr 23;8(4):e62002. doi: 10.1371/journal.pone.0062002. Print 2013.
Cancer stem cells contribute to the malignant phenotypes of a variety of cancers, but markers to identify human hypopharyngeal cancer (HPC) stem cells remain poorly understood. Here, we report that the CD271(+) population sorted from xenotransplanted HPCs possesses an enhanced tumor-initiating capability in immunodeficient mice. Tumors generated from the CD271(+) cells contained both CD271(+) and CD271(-) cells, indicating that the population could undergo differentiation. Immunohistological analyses of the tumors revealed that the CD271(+) cells localized to a perivascular niche near CD34(+) vasculature, to invasive fronts, and to the basal layer. In accordance with these characteristics, a stemness marker, Nanog, and matrix metalloproteinases (MMPs), which are implicated in cancer invasion, were significantly up-regulated in the CD271(+) compared to the CD271 (-) cell population. Furthermore, using primary HPC specimens, we demonstrated that high CD271 expression was correlated with a poor prognosis for patients. Taken together, our findings indicate that CD271 is a novel marker for HPC stem-like cells and for HPC prognosis.
癌症干细胞有助于多种癌症的恶性表型,但鉴定人下咽癌(HPC)干细胞的标志物仍知之甚少。在这里,我们报告说,从异种移植的 HPC 中分选的 CD271(+)群体在免疫缺陷小鼠中具有增强的肿瘤起始能力。来自 CD271(+)细胞的肿瘤既含有 CD271(+)细胞又含有 CD271(-)细胞,表明该群体能够进行分化。对肿瘤的免疫组织化学分析表明,CD271(+)细胞定位于靠近 CD34(+)血管的血管周围龛位、侵袭前沿和基底层。与这些特征一致,干细胞标志物 Nanog 和基质金属蛋白酶(MMPs)在上调与 CD271(-)细胞群体相比,CD271(+)细胞中显著上调,这些 MMPs与癌症侵袭有关。此外,使用原发性 HPC 标本,我们证明高 CD271 表达与患者预后不良相关。综上所述,我们的研究结果表明,CD271 是 HPC 类干细胞和 HPC 预后的新型标志物。