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PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization

The PDZ-LIM domain-containing protein 2 (PDLIM2) regulates cell polarity and the protein stability of key transcription factors in epithelial and hemopoietic cells. We previously reported that PDLIM2 is more highly expressed in Triple Negative Breast Cancer (TNBC) than in other breast cancer types o...

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Autores principales: Cox, Orla T., O’Sullivan, Neil, Tresse, Emilie, Ward, Stephanie, Buckley, Niamh, O’Connor, Rosemary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9749823/
https://www.ncbi.nlm.nih.gov/pubmed/36531051
http://dx.doi.org/10.3389/fonc.2022.1028959
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author Cox, Orla T.
O’Sullivan, Neil
Tresse, Emilie
Ward, Stephanie
Buckley, Niamh
O’Connor, Rosemary
author_facet Cox, Orla T.
O’Sullivan, Neil
Tresse, Emilie
Ward, Stephanie
Buckley, Niamh
O’Connor, Rosemary
author_sort Cox, Orla T.
collection PubMed
description The PDZ-LIM domain-containing protein 2 (PDLIM2) regulates cell polarity and the protein stability of key transcription factors in epithelial and hemopoietic cells. We previously reported that PDLIM2 is more highly expressed in Triple Negative Breast Cancer (TNBC) than in other breast cancer types or normal breast tissue. In the course of the TNBC study, it was noted that PDLIM2 was highly expressed in the stroma of PDLIM2-expressing tumours. Here, we investigated the phenotype of these stromal cells and whether any infiltrating immune population was linked to PDLIM2 expression. We found that high PDLIM2 expression in breast tumours was associated with higher levels of infiltrating M2 macrophages, but was not associated with infiltrating T cell sub-populations. We then tested whether PDLIM2 contributes to macrophage differentiation or function by using cultures of bone marrow-derived macrophages from wildtype and Pdlim2 knockout mice. This demonstrated that PDLIM2 is required for naïve macrophage migration and for the full adoption of IL-4-induced M2 polarization, including expression of M2 phenotypic markers, cell adhesion and cell migration. TLR4-, TLR3- or IFNγ-induced M1 macrophage activity was less dependent on PDLIM2. Finally, analysis of publicly available breast cancer datasets showed that high PDLIM2 expression is associated with increased M2 macrophage infiltration. We conclude that PDLIM2 expression influences the tumour associated stroma and, in particular, M2 macrophage infiltration that may contribute to the progression of TNBC or other subsets of breast cancer.
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spelling pubmed-97498232022-12-15 PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization Cox, Orla T. O’Sullivan, Neil Tresse, Emilie Ward, Stephanie Buckley, Niamh O’Connor, Rosemary Front Oncol Oncology The PDZ-LIM domain-containing protein 2 (PDLIM2) regulates cell polarity and the protein stability of key transcription factors in epithelial and hemopoietic cells. We previously reported that PDLIM2 is more highly expressed in Triple Negative Breast Cancer (TNBC) than in other breast cancer types or normal breast tissue. In the course of the TNBC study, it was noted that PDLIM2 was highly expressed in the stroma of PDLIM2-expressing tumours. Here, we investigated the phenotype of these stromal cells and whether any infiltrating immune population was linked to PDLIM2 expression. We found that high PDLIM2 expression in breast tumours was associated with higher levels of infiltrating M2 macrophages, but was not associated with infiltrating T cell sub-populations. We then tested whether PDLIM2 contributes to macrophage differentiation or function by using cultures of bone marrow-derived macrophages from wildtype and Pdlim2 knockout mice. This demonstrated that PDLIM2 is required for naïve macrophage migration and for the full adoption of IL-4-induced M2 polarization, including expression of M2 phenotypic markers, cell adhesion and cell migration. TLR4-, TLR3- or IFNγ-induced M1 macrophage activity was less dependent on PDLIM2. Finally, analysis of publicly available breast cancer datasets showed that high PDLIM2 expression is associated with increased M2 macrophage infiltration. We conclude that PDLIM2 expression influences the tumour associated stroma and, in particular, M2 macrophage infiltration that may contribute to the progression of TNBC or other subsets of breast cancer. Frontiers Media S.A. 2022-11-30 /pmc/articles/PMC9749823/ /pubmed/36531051 http://dx.doi.org/10.3389/fonc.2022.1028959 Text en Copyright © 2022 Cox, O’Sullivan, Tresse, Ward, Buckley and O’Connor https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Cox, Orla T.
O’Sullivan, Neil
Tresse, Emilie
Ward, Stephanie
Buckley, Niamh
O’Connor, Rosemary
PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization
title PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization
title_full PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization
title_fullStr PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization
title_full_unstemmed PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization
title_short PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization
title_sort pdlim2 is highly expressed in breast cancer tumour-associated macrophages and is required for m2 macrophage polarization
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9749823/
https://www.ncbi.nlm.nih.gov/pubmed/36531051
http://dx.doi.org/10.3389/fonc.2022.1028959
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