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Secretion of BMP-2 by tumorassociated macrophages (TAM) promotes microcalcifcations in breast cancer

Breast microcalcifcations is a characteristic feature in diagnostic imaging and a prognostic factor of breast cancer. However, the underlying mechanisms of breast microcalcifcations formation are not fully understood. Previous studies have shown that upregulation of bone morphogenetic protein 2 (BMP-2) is associated with the occurrence of microcalcifcations and tumor-associated macrophages (TAMs) in the tumor microenvironment can secrete BMP-2. | Wang et al. BMC Cancer 2022 22 34 https doi.org 10.1186 s12885-021-09150-3 RESEARCH Open Access Secretion of BMP-2 by tumor- associated macrophages TAM promotes microcalcifications in breast cancer Shuo Wang1 Haiyang Jiang1 Caiwei Zheng2 Ming Gu1 and Xinyu Zheng1 3 Abstract 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 microcalcifica- tions 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 tis- sues 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