Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Discov. 2011 Dec;1(7):580-6. doi: 10.1158/2159-8290.CD-11-0215. Epub 2011 Nov 3.
Metastasis is a complex, multistep process that begins with the epithelial-mesenchymal transition (EMT). Circulating tumor cells (CTC) are believed to have undergone EMT and thus lack or express low levels of epithelial markers commonly used for enrichment and/or detection of such cells. However, most current CTC detection methods target only EpCAM and/or cytokeratin (CK) to enrich epithelial CTCs, resulting in failure to recognize other, perhaps more important, CTC phenotypes that lack expression of these markers. Here, we describe a population of complex aneuploid CTCs that do not express CK or CD45 antigen in patients with breast, ovarian, or colorectal cancer. These cells were not observed in healthy subjects. We show that the primary epithelial tumors were characterized by similar complex aneuploidy, indicating conversion to an EMT phenotype in the captured cells. Collectively, our study provides a new method for highly efficient capture of previously unrecognized populations of CTCs.
Current assays for CTC capture likely miss populations of cells that have undergone EMT. Capture and study of CTCs that have undergone EMT would allow a better understanding of the mechanisms driving metastasis.
转移是一个复杂的多步骤过程，始于上皮-间充质转化（EMT）。循环肿瘤细胞（CTC）被认为已经经历了 EMT，因此缺乏或表达低水平的上皮标志物，这些标志物通常用于此类细胞的富集和/或检测。然而，大多数当前的 CTC 检测方法仅针对 EpCAM 和/或细胞角蛋白（CK）来富集上皮 CTC，导致无法识别其他可能更重要的 CTC 表型，这些表型缺乏这些标志物的表达。在这里，我们描述了一群在患有乳腺癌、卵巢癌或结直肠癌的患者中不表达 CK 或 CD45 抗原的复杂非整倍体 CTC。这些细胞在健康受试者中未观察到。我们表明，主要上皮肿瘤的特征是类似的复杂非整倍性，表明在捕获的细胞中发生 EMT 表型转化。总的来说，我们的研究提供了一种高效捕获以前未被识别的 CTC 群体的新方法。
目前用于 CTC 捕获的检测方法可能会错过已经经历 EMT 的细胞群体。对经历 EMT 的 CTC 的捕获和研究将有助于更好地理解驱动转移的机制。
