Arch Immunol Ther Exp (Warsz). 2014 Feb;62(1):67-75. doi: 10.1007/s00005-013-0250-1.
Lung tumors are characterized by their high metastatic potential, which is the main cause of therapeutic failure. However, the exact cellular origin of metastasis remains unknown. Since the introduction of the cancer stem cell theory, lung cancer stem cells (LCSCs) have been thought to represent metastasis-founding cells. The current study aimed to evaluate whether LCSCs could be found in the circulation. Expression of the stem cell markers CD133 and EpCAM was confirmed in tumor and normal lung tissue by flow cytometry. Then, this technique was further used to investigate the expression of CD133 and EpCAM in the peripheral blood of 41 patients with primary lung cancer. Putative LCSCs (CD133?EpCAM?) were present in 6/7 tumor samples, and CD133?EpCAM? cells were identified in the blood samples of 15 patients at a median level of 40/ml of blood. EpCAM? cells were detected in 60 % of the patients, and the number of these cells was higher in patients with adenocarcinoma than patients with squamous cell carcinoma and was also higher in patients with less advanced disease. Moreover, the frequency of this subpopulation significantly correlated with the circulating level of SSEA-4? cells. Additionally, CD133?EpCAM- cells were found in 87 % of the patients, and the numbers of these cells were significantly higher in patients with distant metastases and correlated with disease stage. This study confirmed the presence of an LCSC subpopulation with a CD133?EpCAM? phenotype in the tumors and blood of patients with lung cancer, and these results suggest an important role for CD133 and EpCAM in lung cancer progression and their potential application as novel biomarkers of the disease.
肺肿瘤的特征是其高转移潜能，这是治疗失败的主要原因。然而，转移的确切细胞起源仍然未知。自从癌症干细胞理论问世以来，肺癌干细胞（LCSC）被认为代表了转移起始细胞。本研究旨在评估循环中是否存在 LCSC。通过流式细胞术证实了肿瘤和正常肺组织中干细胞标志物 CD133 和 EpCAM 的表达。然后，该技术进一步用于研究 41 例原发性肺癌患者外周血中 CD133 和 EpCAM 的表达。在 7 个肿瘤样本中有 6 个存在推定的 LCSC（CD133?EpCAM?），在 15 例患者的血液样本中以中位数 40/ml 的血液水平鉴定出 CD133?EpCAM?细胞。在 60%的患者中检测到 EpCAM?细胞，在腺癌患者中的数量高于鳞状细胞癌患者，在疾病进展程度较低的患者中也更高。此外，该亚群的频率与循环中 SSEA-4?细胞的水平显著相关。此外，在 87%的患者中发现了 CD133?EpCAM-细胞，这些细胞的数量在远处转移患者中明显更高，并与疾病分期相关。本研究证实了肺癌患者肿瘤和血液中存在具有 CD133?EpCAM?表型的 LCSC 亚群，这些结果表明 CD133 和 EpCAM 在肺癌进展中具有重要作用，并且它们可能作为该疾病的新型生物标志物得到应用。
