CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues.
CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues.
复制标题
DOI：
10.1158/2159-8290.cd-12-0107
复制
发表时间：
2012-09
期刊：
影响因子：
28.2
通讯作者：
Tlsty TD
中科院分区：
文献类型：
--
作者：
DeFilippis RA;Chang H;Dumont N;Rabban JT;Chen YY;Fontenay GV;Berman HK;Gauthier ML;Zhao J;Hu D;Marx JJ;Tjoe JA;Ziv E;Febbraio M;Kerlikowske K;Parvin B;Tlsty TD
虽然高钼靶密度(MD)被认为是浸润性乳腺癌的最强危险因素之一，但参与调节这一临床特征的基因尚不清楚。高MD的组织与肿瘤组织的恶性病变中的间质成分具有关键的组织学特征，特别是低脂肪细胞和高ECM含量。我们发现，CD36是一种跨膜受体，它协调调节包括脂肪细胞分化、血管生成、细胞-ECM相互作用和免疫信号在内的多种促肿瘤表型，在与高MD和肿瘤间质相关的多种细胞类型的无病间质中受到极大抑制。使用体外和体内试验，我们证明CD36抑制是必要的和充分的，以概括上述在高MD和肿瘤组织中观察到的表型。与这一协调程序在肿瘤发生中的功能作用一致，我们观察到临床结果与CD36的表达密切相关。
Although high mammographic density (MD) is considered one of the strongest risk factors for invasive breast cancer, the genes involved in modulating this clinical feature are unknown. Tissues of high MD share key histological features with stromal components within malignant lesions of tumor tissues, specifically low adipocyte and high ECM content. We show that CD36, a transmembrane receptor that coordinately modulates multiple pro-tumorigenic phenotypes including adipocyte differentiation, angiogenesis, cell-ECM interactions, and immune signaling, is greatly repressed in multiple cell types of disease-free stroma associated with high MD and tumor stroma. Using both in vitro and in vivo assays, we demonstrate that CD36 repression is necessary and sufficient to recapitulate the abovementioned phenotypes observed in high MD and tumor tissues. Consistent with a functional role for this coordinated program in tumorigenesis, we observe that clinical outcomes are strongly associated with CD36 expression.