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

肿瘤相关巨噬细胞 (TAM) 分泌 BMP-2 促进乳腺癌微钙化

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作者:Shuo Wang, Haiyang Jiang, Caiwei Zheng, Ming Gu, Xinyu Zheng

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.

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.

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