MicroRNA-200c Attenuates the Tumor-Infiltrating Capacity of Macrophages

Macrophages constitute a major part of the tumor-infiltrating immune cells. Within the tumor microenvironment, they acquire an alternatively activated, tumor-supporting phenotype. Factors released by tumor cells are crucial for the recruitment of tumor-associated macrophages. In the present project,...

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Detalles Bibliográficos
Autores: Raue, Rebecca, Frank, Ann-Christin, Fuhrmann, Dominik C., Cruz, Patricia de la, Rösser, Silvia, Bauer, Rebekka, Cardamone, Giulia, Weigert, Andreas, Syed, Shahzad Nawaz, Schmid, Tobias, Brüne, Bernhard
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/306755
Acceso en línea:http://hdl.handle.net/10261/306755
https://api.elsevier.com/content/abstract/scopus_id/85125271681
Access Level:acceso abierto
Palabra clave:Breast tumor
Macrophage
miR
Tumor microenvironment
Descripción
Sumario:Macrophages constitute a major part of the tumor-infiltrating immune cells. Within the tumor microenvironment, they acquire an alternatively activated, tumor-supporting phenotype. Factors released by tumor cells are crucial for the recruitment of tumor-associated macrophages. In the present project, we aimed to understand the role of hsa-miR-200c-3p (miR-200c) in the interplay between tumor cells and macrophages. To this end, we employed a coculture system of MCF7 breast tumor cells and primary human macrophages and observed the transfer of miR-200c from apoptotic tumor cells to macrophages, which required intact CD36 receptor in macrophages. We further comprehensively determined miR-200c targets in macrophages by mRNA-sequencing and identified numerous migration-associated mRNAs to be downregulated by miR-200c. Consequently, miR-200c attenuated macrophage infiltration into 3-dimensional tumor spheroids. miR-200c-mediated reduction in infiltration further correlated with a miR-200c migration signature comprised of the four miR-200c-repressed, predicted targets PPM1F, RAB11FIB2, RDX, and MSN.