Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites.,Oncogene

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Single-cell EMT-related transcriptional analysis revealed intra-cluster heterogeneity of tumor cell clusters in epithelial ovarian cancer ascites.
Oncogene ( IF 6.9 ) Pub Date : 2020-04-13 , DOI: 10.1038/s41388-020-1288-2
Tongtong Kan ₁ , Wei Wang ₁ , Philip P Ip ₂ , Shengtao Zhou ₃ , Alice S Wong ₄ , Xin Wang ₁ , Mengsu Yang _{1,

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Affiliation

Malignant ascites of epithelial ovarian cancer is a metastatic tumor microenvironment in which large amounts of disseminated single cells (DSCs) and disseminated tumor cell clusters (DTCCs) are commonly observed. The tumor cell clusters are known to be more aggressive than individual tumor cells in cancer metastasis; however, little is known about the mechanism. Applying single-cell epithelial-to-mesenchymal transition (EMT)-related transcriptional analysis in 120 DSCs and 195 intra-cluster cells from 27 DTCCs, we demonstrated that DTCCs were heterogeneous cellular units comprised of epithelial tumor cells, leukocytes, and cancer-associated fibroblasts (CAFs). Through the analysis of intra-DTCC heterogeneity, we identified that CAFs induced EMT of tumor cells via TGFβ signaling within the DTCC microenvironment. The activation of EMT program, in particular the upregulation of ZEB2, enabled the acquisition of additional chemoresistance and metastasis abilities of the intra-DTCC tumor cells, which resulted in the aggressiveness of DTCCs.

中文翻译：

单细胞EMT相关的转录分析揭示了上皮性卵巢癌腹水中肿瘤细胞簇的簇内异质性。

上皮性卵巢癌的恶性腹水是一种转移性肿瘤微环境，通常观察到大量的弥散性单细胞（DSC）和弥散性肿瘤细胞簇（DTCC）。已知肿瘤细胞簇在癌症转移中比单个肿瘤细胞更具攻击性。但是，对该机制知之甚少。在27个DTCC的120个DSC和195个集群内细胞中应用单细胞上皮到间充质转化（EMT）相关的转录分析，我们证明了DTCC是由上皮肿瘤细胞，白细胞和癌症相关的异质细胞单位成纤维细胞（CAF）。通过内部DTCC异质性的分析，我们确定CAF通过DTCC微环境中的TGFβ信号传导诱导肿瘤细胞的EMT。激活EMT程序，

更新日期：2020-04-13

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