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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1028959/full |
| _version_ | 1811289948431581184 |
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| author | Orla T. Cox Neil O’Sullivan Emilie Tresse Stephanie Ward Niamh Buckley Rosemary O’Connor |
| author_facet | Orla T. Cox Neil O’Sullivan Emilie Tresse Stephanie Ward Niamh Buckley Rosemary O’Connor |
| author_sort | Orla T. Cox |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T04:04:21Z |
| format | Article |
| id | doaj.art-4035ff74f52a483a9faba202d1a5fca0 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T04:04:21Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4035ff74f52a483a9faba202d1a5fca02022-12-22T03:03:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10289591028959PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarizationOrla T. Cox0Neil O’Sullivan1Emilie Tresse2Stephanie Ward3Niamh Buckley4Rosemary O’Connor5Cell Biology Laboratory, School of Biochemistry and Cell Biology, BioSciences Institute, University College Cork, Cork, IrelandCell Biology Laboratory, School of Biochemistry and Cell Biology, BioSciences Institute, University College Cork, Cork, IrelandCell Biology Laboratory, School of Biochemistry and Cell Biology, BioSciences Institute, University College Cork, Cork, IrelandCell Biology Laboratory, School of Biochemistry and Cell Biology, BioSciences Institute, University College Cork, Cork, IrelandSchool of Pharmacy and Patrick G. Johnson Centre for Cancer Research, Queens University, Belfast, United KingdomCell Biology Laboratory, School of Biochemistry and Cell Biology, BioSciences Institute, University College Cork, Cork, IrelandThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.1028959/fullTriple Negative Breast Cancer (TNBC)PDLIM2M2 macrophagecell differentiationimmune infiltration |
| spellingShingle | Orla T. Cox Neil O’Sullivan Emilie Tresse Stephanie Ward Niamh Buckley Rosemary O’Connor PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization Frontiers in Oncology Triple Negative Breast Cancer (TNBC) PDLIM2 M2 macrophage cell differentiation immune infiltration |
| 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 | Triple Negative Breast Cancer (TNBC) PDLIM2 M2 macrophage cell differentiation immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1028959/full |
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