Department of Integrative Medicine for Longevity, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, 920-8641, Japan.
CREST, Japan Science and Technology Agency, Tokyo, 102-0076, Japan.
Sci Rep. 2017 Oct 27;7(1):14225. doi: 10.1038/s41598-017-14676-3.
Single cell transcriptome analysis of a cancer tissue can provide objective assessment of subtype population or the activation of each of various microenvironment component cells. In this study, we applied our newly developed technique of single cell analysis to the myometrial infiltration side (M-side) and the endometrial side (E-side) of a human endometrioid adenocarcinoma with squamous differentiation tissues. We also analyzed spherogenic cultures derived from the same tissue to identify putative regulators of stemness in vivo. Cancer cells in the E-side were highly malignant compared with those in the M-side. Many cells on the E-side were positive for spheroid-specific tumorigenesis-related markers including SOX2. In addition, there were higher numbers of epithelial-to-mesenchymal transition (EMT) cells in the E-side compared with the M-side. This study identified a site containing cells with high malignant potential such as EMT and cancer stem-like cells in cancer tissues. Finally, we demonstrate that established endometrioid adenocarcinoma subtype classifiers were variably expressed across individual cells within a tumor. Thus, such intratumoral heterogeneity may be related to prognostic implications.
对癌症组织的单细胞转录组分析可以提供对亚群人群或各种微环境成分细胞的激活的客观评估。在这项研究中，我们将我们新开发的单细胞分析技术应用于具有鳞状分化的人类子宫内膜样腺癌的子宫肌层浸润侧（M 侧）和子宫内膜侧（E 侧）组织。我们还分析了源自同一组织的球体培养物，以鉴定体内干性的潜在调节因子。E 侧的癌细胞比 M 侧的恶性程度更高。E 侧的许多细胞呈球体特异性肿瘤发生相关标志物阳性，包括 SOX2。此外，E 侧的上皮-间充质转化（EMT）细胞数量多于 M 侧。这项研究在癌症组织中确定了一个包含高恶性潜能的细胞的部位，如 EMT 和癌症干细胞样细胞。最后，我们证明，在肿瘤内的单个细胞中，已建立的子宫内膜样腺癌亚型分类器的表达是不同的。因此，这种肿瘤内异质性可能与预后有关。
