Tumor-associated macrophages (TAMs) depend on ZEB1 for their cancer-promoting roles
| Autor: | Cortés, Marlies, Sanchez-Moral, Lidia, de Barrios, Oriol, Fernández-Aceñero, María J, Martínez-Campanario, M C, Esteve-Codina, Anna, Darling, Douglas S, Győrffy, Balázs, Lawrence, Toby, Dean, Douglas C, Postigo, Antonio |
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| Rok vydání: | 2017 |
| Předmět: |
Carcinogenesis
Receptors CCR2 TAMs Cell Count Models Biological Monocytes stomatognathic system Colony-Stimulating Factors Neoplasms ZEB1 tumor microenvironment Animals Humans skin and connective tissue diseases Chemokine CCL2 Ovarian Neoplasms Macrophages EMT Histocompatibility Antigens Class II Zinc Finger E-box-Binding Homeobox 1 Cell Differentiation Macrophage Activation Survival Analysis Up-Regulation Antigens Differentiation B-Lymphocyte Gene Expression Regulation Neoplastic Mice Inbred C57BL Disease Models Animal Phenotype Matrix Metalloproteinase 9 Drug Resistance Neoplasm Disease Progression Female hormones hormone substitutes and hormone antagonists |
| Zdroj: | Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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