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Tumor-associated macrophages (TAMs) depend on ZEB1 for their cancer-promoting roles
Authors
Anna Esteve‐Codina
Antonio Postigo
+10 more
Balázs Győrffy
Douglas C Dean
Douglas S Darling
Lidia Sanchez‐Moral
Marlies Cortés
María J Fernández‐Aceñero
MC Martínez‐Campanario
Oriol de Barrios
Takagi T
Toby Lawrence
Publication date
28 August 2018
Publisher
'EMBO'
Doi
Cite
Abstract
Accumulation of tumor-associated macrophages (TAMs) associates with malignant progression in cancer. However, the mechanisms that drive the pro-tumor functions of TAMs are not fully understood. ZEB1 is best known for driving an epithelial-to-mesenchymal transition (EMT) in cancer cells to promote tumor progression. However, a role for ZEB1 in macrophages and TAMs has not been studied. Here we describe that TAMs require ZEB1 for their tumor-promoting and chemotherapy resistance functions in a mouse model of ovarian cancer. Only TAMs that expressed full levels of Zeb1 accelerated tumor growth. Mechanistically, ZEB1 expression in TAMs induced their polarization toward an F4/80low pro-tumor phenotype, including direct activation of Ccr2. In turn, expression of ZEB1 by TAMs induced Ccl2, Cd74, and a mesenchymal/stem-like phenotype in cancer cells. In human ovarian carcinomas, TAM infiltration and CCR2 expression correlated with ZEB1 in tumor cells, where along with CCL2 and CD74 determined poorer prognosis. Importantly, ZEB1 in TAMs was a factor of poorer survival in human ovarian carcinomas. These data establish ZEB1 as a key factor in the tumor microenvironment and for maintaining TAMs’ tumor-promoting functions. © 2017 The Author
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oai:repo.lib.semmelweis.hu:123...
Last time updated on 05/11/2018
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info:doi/10.15252%2Fembj.20179...
Last time updated on 03/01/2020