间充质干细胞
趋化因子
癌症研究
炎症性乳腺癌
旁分泌信号
癌症干细胞
乳腺癌
自分泌信号
转移
生物
癌细胞
免疫系统
免疫学
癌症
干细胞
细胞生物学
细胞培养
受体
生物化学
遗传学
作者
Amanda Valeta-Magara,Abhilash Gadi,Viviana Volta,Beth Walters,Rezina Arju,Shah Giashuddin,Hua Zhong,Robert J. Schneider
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2019-07-01
卷期号:79 (13): 3360-3371
被引量:86
标识
DOI:10.1158/0008-5472.can-17-2158
摘要
Abstract Inflammatory breast cancer (IBC) is a highly aggressive form of breast cancer that displays profound cancer stem cell (CSC) and mesenchymal features that promote rapid metastasis. Another hallmark of IBC is high infiltration of M2 tumor-associated (immune-suppressing) macrophages. The molecular mechanism that drives these IBC phenotypes is not well understood. Using patient breast tumor specimens, breast cancer cell lines, and a patient-derived xenograft model of IBC, we demonstrate that IBC strongly expresses IL8 and growth-regulated oncogene (GRO) chemokines that activate STAT3, which promotes development of high levels of CSC-like cells and a mesenchymal phenotype. We also show that IBC expresses high levels of many monocyte recruitment and macrophage polarization factors that attract and differentiate monocytes into tumor-promoting, immune-suppressing M2-like macrophages. The M2 macrophages in turn were found to secrete high levels of IL8 and GRO chemokines, thereby creating a feed-forward chemokine loop that further drives an IBC epithelial-to-mesenchymal transition. Our study uncovers an intricate IBC-initiated autocrine–paracrine signaling network between IBC cells and monocytes that facilitates development of this highly aggressive form of breast cancer. Significance: This study uncovers a signaling network in which IBC cells commandeer macrophages to become tumor-promoting, and they in turn drive IBC cells to be more cancer stem-like, mesenchymal, and aggressive.
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