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Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer

INTRODUCTION: Breast microcalcifications is a characteristic feature in diagnostic imaging and a prognostic factor of breast cancer. However, the underlying mechanisms of breast microcalcifications formation are not fully understood. Previous studies have shown that upregulation of bone morphogeneti...

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Autores principales: Wang, Shuo, Jiang, Haiyang, Zheng, Caiwei, Gu, Ming, Zheng, Xinyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729115/
https://www.ncbi.nlm.nih.gov/pubmed/34983451
http://dx.doi.org/10.1186/s12885-021-09150-3
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author Wang, Shuo
Jiang, Haiyang
Zheng, Caiwei
Gu, Ming
Zheng, Xinyu
author_facet Wang, Shuo
Jiang, Haiyang
Zheng, Caiwei
Gu, Ming
Zheng, Xinyu
author_sort Wang, Shuo
collection PubMed
description INTRODUCTION: Breast microcalcifications is a characteristic feature in diagnostic imaging and a prognostic factor of breast cancer. However, the underlying mechanisms of breast microcalcifications formation are not fully understood. Previous studies have shown that upregulation of bone morphogenetic protein 2 (BMP-2) is associated with the occurrence of microcalcifications and tumor-associated macrophages (TAMs) in the tumor microenvironment can secrete BMP-2. The aim of this study is to elucidate the role of secretion of BMP-2 by TAMs in promoting microcalcifications of breast cancer through immunohistochemical staining and co-culturing of breast cancer cells with TAMs. METHODS: A total of 272 patients diagnosed with primary invasive breast cancer from January 2010 to January 2012 in the First Hospital of China Medical University were included in this study. Immunohistochemical staining of CD68 (marker of entire macrophages), CD168 (marker of the M2-like macrophages) and BMP-2 were performed on 4-μm tissue microarray (TMA) sections. Following induction, THP-1 cells were differentiated to M2-like TAMs and were then co-cultured with breast cancer cells (MCF-7). Calcifications and BMP-2 expression were analyzed by Alizarin Red S staining and western blot, respectively. RESULTS: Immunohistochemical analysis showed that the expression of CD168 was significantly increased in tissues with microcalcifications and was correlated with the expression of BMP-2 and poor prognosis. The formation of cellular microcalcifications and BMP-2 expression were significantly increased in MCF-7 cells co-cultured with TAMs compared with MCF-7 cells alone. CONCLUSIONS: These findings support the hypothesis that TAMs secrete BMP-2 to induce microcalcifications in breast cancer cells and influence prognosis via multiple pathways including BMP-2 and its downstream factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09150-3.
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spelling pubmed-87291152022-01-07 Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer Wang, Shuo Jiang, Haiyang Zheng, Caiwei Gu, Ming Zheng, Xinyu BMC Cancer Research INTRODUCTION: Breast microcalcifications is a characteristic feature in diagnostic imaging and a prognostic factor of breast cancer. However, the underlying mechanisms of breast microcalcifications formation are not fully understood. Previous studies have shown that upregulation of bone morphogenetic protein 2 (BMP-2) is associated with the occurrence of microcalcifications and tumor-associated macrophages (TAMs) in the tumor microenvironment can secrete BMP-2. The aim of this study is to elucidate the role of secretion of BMP-2 by TAMs in promoting microcalcifications of breast cancer through immunohistochemical staining and co-culturing of breast cancer cells with TAMs. METHODS: A total of 272 patients diagnosed with primary invasive breast cancer from January 2010 to January 2012 in the First Hospital of China Medical University were included in this study. Immunohistochemical staining of CD68 (marker of entire macrophages), CD168 (marker of the M2-like macrophages) and BMP-2 were performed on 4-μm tissue microarray (TMA) sections. Following induction, THP-1 cells were differentiated to M2-like TAMs and were then co-cultured with breast cancer cells (MCF-7). Calcifications and BMP-2 expression were analyzed by Alizarin Red S staining and western blot, respectively. RESULTS: Immunohistochemical analysis showed that the expression of CD168 was significantly increased in tissues with microcalcifications and was correlated with the expression of BMP-2 and poor prognosis. The formation of cellular microcalcifications and BMP-2 expression were significantly increased in MCF-7 cells co-cultured with TAMs compared with MCF-7 cells alone. CONCLUSIONS: These findings support the hypothesis that TAMs secrete BMP-2 to induce microcalcifications in breast cancer cells and influence prognosis via multiple pathways including BMP-2 and its downstream factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09150-3. BioMed Central 2022-01-04 /pmc/articles/PMC8729115/ /pubmed/34983451 http://dx.doi.org/10.1186/s12885-021-09150-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Shuo
Jiang, Haiyang
Zheng, Caiwei
Gu, Ming
Zheng, Xinyu
Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer
title Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer
title_full Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer
title_fullStr Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer
title_full_unstemmed Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer
title_short Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer
title_sort secretion of bmp-2 by tumor-associated macrophages (tam) promotes microcalcifications in breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8729115/
https://www.ncbi.nlm.nih.gov/pubmed/34983451
http://dx.doi.org/10.1186/s12885-021-09150-3
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