Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo.
Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo.
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DOI：
10.1186/1471-2407-11-529
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发表时间：
2011-12-30
期刊：
影响因子：
3.8
通讯作者：
Kandel JJ
中科院分区：
文献类型：
--
作者：
Anastassiou D;Rumjantseva V;Cheng W;Huang J;Canoll PD;Yamashiro DJ;Kandel JJ
癌细胞运动性和侵袭性的生物学机制尚不清楚，尽管已经假设它们涉及某种类型的上皮-间质转化（EMT）。我们在免疫功能低下的小鼠中使用人类癌细胞的异种移植模型，用物种特异性探针分别对收获的肿瘤进行分析，并对结果进行计算分析。在这里，我们发现人类癌细胞在体内表达一种精确的多癌侵袭相关基因表达特征，主要包括许多EMT标记物，其中包括转录因子Slug，纤连蛋白和α-SMA。我们发现，人类，而不是小鼠，细胞表达的签名和鼻涕虫是唯一上调EMT诱导转录因子。该签名也存在于许多公开的癌症基因表达数据集的样本中，表明它是由多种癌症类型的癌细胞本身产生的，包括非上皮性癌症，如神经母细胞瘤。此外，我们发现，在人类异种移植细胞中的签名的存在与浸润性肿瘤附近的小鼠组织中脂肪细胞标志物的下调有关，这表明当癌细胞遇到脂肪细胞时，签名是由上下文微环境相互作用触发的，如先前所报道的。这种癌症间充质转化特征的已知、精确和一致的基因组成，特别是当与相邻微环境的同时分析相结合时，为阐明癌症侵袭性的潜在机制以及鉴定潜在的诊断标志物和转移抑制治疗的靶点提供了独特的机会。
The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT). We used xenograft models of human cancer cells in immunocompromised mice, profiling the harvested tumors separately with species-specific probes and computationally analyzing the results. Here we show that human cancer cells express in vivo a precise multi-cancer invasion-associated gene expression signature that prominently includes many EMT markers, among them the transcription factor Slug, fibronectin, and α-SMA. We found that human, but not mouse, cells express the signature and Slug is the only upregulated EMT-inducing transcription factor. The signature is also present in samples from many publicly available cancer gene expression datasets, suggesting that it is produced by the cancer cells themselves in multiple cancer types, including nonepithelial cancers such as neuroblastoma. Furthermore, we found that the presence of the signature in human xenografted cells was associated with a downregulation of adipocyte markers in the mouse tissue adjacent to the invasive tumor, suggesting that the signature is triggered by contextual microenvironmental interactions when the cancer cells encounter adipocytes, as previously reported. The known, precise and consistent gene composition of this cancer mesenchymal transition signature, particularly when combined with simultaneous analysis of the adjacent microenvironment, provides unique opportunities for shedding light on the underlying mechanisms of cancer invasiveness as well as identifying potential diagnostic markers and targets for metastasis-inhibiting therapeutics.
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影响因子：
11.2
作者：
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DOI：
10.1073/pnas.091062498
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发表时间：
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