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研究探明间质微环境塑造胰腺癌的肿瘤内结构
作者:小柯机器人 发布时间:2019/7/27 10:15:33

马萨诸塞州综合医院David T. Ting研究组宣布他们揭示了基质微环境形成胰腺癌的瘤内结构。相关论文发表在2019年5月30日出版的《细胞》杂志上。

研究者在胰腺癌(胰腺导管腺癌[PDAC])模型系统中,结合单细胞RNA和蛋白质分析技术,研究基质肿瘤相关成纤维细胞(CAFs)调控异质性中的作用。研究小组发现,单细胞群体分布十分明显地偏向侵袭性上皮-间质转分化(EMT)和增殖(PRO)表型(这些表型与丝裂原激活蛋白激酶-MAPK、信号转导因子和转录激活因子3-STAT3信号传导有关)。该课题组研究人员利用RNA原位杂交高通量数字图像技术,采集了195例PDAC肿瘤信息,进而对319,626个癌细胞进行了EMT和PRO亚群量化分析,使得这些细胞可以在不同的肿瘤腺体“单元”中进行分类。肿瘤腺体分型提供了额外的关于肿瘤内部异质性的信息,这些信息与基质丰度和临床结果的差异有关。研究结果证明了人类PDAC中,肿瘤基质通过改变肿瘤腺体的内在模式来影响肿瘤结构的形成。

据介绍,单细胞技术已经描述了组织间的异质性,但驱动单细胞表型的空间分布及原因尚未得到很好的解释。

附:英文原文

Title: Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer

Author: Matteo Ligorio, Srinjoy Sil, Jose Malagon-Lopez, Wilhelm Haas, Martin J. Aryee, David T. Ting

Issue&Volume:Jun 27, 2019 Volume 178Issue 1

Abstract: Single-cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single-cell phenotypes have not been well defined. Combining single-cell RNA and protein analytics in studying the role of stromal cancer-associated fibroblasts (CAFs) in modulating heterogeneity in pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) model systems, we have identified significant single-cell population shifts toward invasive epithelial-to-mesenchymal transition (EMT) and proliferative (PRO) phenotypes linked with mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling. Using high-content digital imaging of RNA in situ hybridization in 195 PDAC tumors, we quantified these EMT and PRO subpopulations in 319,626 individual cancer cells that can be classified within the context of distinct tumor gland “units.” Tumor gland typing provided an additional layer of intratumoral heterogeneity that was associated with differences in stromal abundance and clinical outcomes. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.

DOI: https://doi.org/10.1016/j.cell.2019.05.012

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30510-0

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/