Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Clin Cancer Res. 2019 Nov 15;25(22):6756-6763. doi: 10.1158/1078-0432.CCR-19-0545. Epub 2019 Aug 5.
The epithelial-to-mesenchymal transition, the major process by which some cancer cells convert from an epithelial phenotype to a mesenchymal one, has been suggested to drive chemo-resistance and/or metastasis in patients with cancer. However, only a few studies have demonstrated the presence of CD45/CD326 doubly-positive cells (CD45/CD326 DPC) in cancer. We deployed a combination of cell surface markers to elucidate the phenotypic heterogeneity in non-small cell lung cancer (NSCLC) cells and identified a new subpopulation that is doubly-positive for epithelial and non-epithelial cell-surface markers in both NSCLC cells and patients' malignant pleural effusions.
We procured a total of 39 patients' samples, solid fresh lung cancer tissues from 21 patients and malignant pleural effusion samples from 18 others, and used FACS and fluorescence microscopy to check their surface markers. We also examined the mutations in patients with known acquired mutations.
Our data revealed that 0.4% to 17.9% of the solid tumor tissue cells and a higher percentage of malignant pleural effusion cells harbored CD45/CD326 DPC expressing both epithelial and nonepithelial surface markers. We selected 3 mutation patients and genetically confirmed that the newly identified cell population really originated from cancer cells. We also found that higher proportions of CD45/CD326 DPC are significantly associated with poor prognosis.
In conclusion, varying percentages of CD45/CD326 DPC exist in both solid cancer tissue and malignant pleural effusion in patients with NSCLC. This CD45/CD326 doubly-positive subpopulation can be an important key to clinical management of patients with NSCLC.
上皮-间充质转化(epithelial-to-mesenchymal transition,EMT)是某些癌细胞从上皮表型转化为间充质表型的主要过程,已被认为可导致癌症患者的化疗耐药和/或转移。然而,只有少数研究表明癌症中存在 CD45/CD326 双阳性细胞(CD45/CD326 double positive cells,CD45/CD326 DPC)。我们采用了一系列细胞表面标志物来阐明非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞的表型异质性,并在 NSCLC 细胞和患者恶性胸腔积液中鉴定出一种新的亚群,该亚群对上皮和非上皮细胞表面标志物均呈双阳性。
我们共采集了 39 名患者的样本,包括 21 名患者的新鲜肺部实体肿瘤组织和 18 名患者的恶性胸腔积液样本,并使用流式细胞术和荧光显微镜检查其表面标志物。我们还检查了已知获得性 突变的患者的 突变。
我们的数据显示,0.4%至 17.9%的实体肿瘤组织细胞和更高比例的恶性胸腔积液细胞表达 CD45/CD326 DPC,同时表达上皮和非上皮表面标志物。我们选择了 3 名 突变患者,并通过遗传方法证实新鉴定的细胞群体确实来源于癌细胞。我们还发现,CD45/CD326 DPC 的比例较高与预后不良显著相关。
总之,在 NSCLC 患者的实体肿瘤组织和恶性胸腔积液中均存在不同比例的 CD45/CD326 DPC。这种 CD45/CD326 双阳性亚群可能是 NSCLC 患者临床管理的重要关键。