间质细胞
生物
结直肠癌
癌症研究
肿瘤微环境
转化生长因子
免疫组织化学
癌症
免疫学
遗传学
肿瘤细胞
细胞生物学
作者
Alexandre Calon,Enza Lonardo,Antoni Berenguer‐Llergo,Elisa Espinet,Xavier Hernando‐Momblona,Mar Iglesias,Marta Sevillano,Sergio Palomo-Ponce,Daniele V.F. Tauriello,Daniel Byrom,Carme Cortina,Clara Morral,Carles Barceló,Sébastien Tosi,Antoni Riéra,Camille Stephan‐Otto Attolini,David Rossell,Elena Sancho,Eduard Batlle
出处
期刊:Nature Genetics
[Springer Nature]
日期:2015-02-23
卷期号:47 (4): 320-329
被引量:845
摘要
Recent molecular classifications of colorectal cancer (CRC) based on global gene expression profiles have defined subtypes displaying resistance to therapy and poor prognosis. Upon evaluation of these classification systems, we discovered that their predictive power arises from genes expressed by stromal cells rather than epithelial tumor cells. Bioinformatic and immunohistochemical analyses identify stromal markers that associate robustly with disease relapse across the various classifications. Functional studies indicate that cancer-associated fibroblasts (CAFs) increase the frequency of tumor-initiating cells, an effect that is dramatically enhanced by transforming growth factor (TGF)-β signaling. Likewise, we find that all poor-prognosis CRC subtypes share a gene program induced by TGF-β in tumor stromal cells. Using patient-derived tumor organoids and xenografts, we show that the use of TGF-β signaling inhibitors to block the cross-talk between cancer cells and the microenvironment halts disease progression.
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