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

BMC Cancer

Ming Gu¹  Shuo Wang¹  Haiyang Jiang¹  Xinyu Zheng²  Caiwei Zheng³ 

[1] Department of Breast Surgery, First Affiliated Hospital, China Medical University, 155 North Nanjing Street, 110001, Shenyang, Liaoning, China;Department of Breast Surgery, First Affiliated Hospital, China Medical University, 155 North Nanjing Street, 110001, Shenyang, Liaoning, China;Lab 1, Cancer Institute, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China;University of Miami Miller School of Medicine, Miami, FL, USA;

关键词: Breast cancer;    Tumor-associated macrophages (TAMs);    Microcalcifications;    BMP-2;    CD163;    CD68;   

DOI  :  10.1186/s12885-021-09150-3

来源: Springer

【 摘 要 】

IntroductionBreast 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.MethodsA 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.ResultsImmunohistochemical 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.ConclusionsThese 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.

【 授权许可】

CC BY