Microcalcifications Drive Breast Cancer Occurrence and Development by Macrophage-Mediated Epithelial to Mesenchymal Transition

微钙化通过巨噬细胞介导的上皮间质转化促进乳腺癌的发生和发展

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作者:Manuel Scimeca, Rita Bonfiglio, Erika Menichini, Loredana Albonici, Nicoletta Urbano, Maria Teresa De Caro, Alessandro Mauriello, Orazio Schillaci, Alessandra Gambacurta, Elena Bonanno

Background

This study aims to investigate: (a) the putative association between the presence of microcalcifications and the expression of both epithelial-to-mesenchymal transition and bone biomarkers, (b) the role of microcalcifications in the breast osteoblast-like cells (BOLCs) formation, and (c) the association between microcalcification composition and breast cancer progression.

Conclusions

Altogether, our data shed new light about the role of microcalcifications in breast cancer occurrence and progression.

Methods

We collected 174 biopsies on which we performed immunohistochemical and ultrastructural analysis. In vitro experiments were performed to demonstrate the relationship among microcalcification, BOLCs development, and breast cancer occurrence. Ex vivo investigations demonstrated the significant increase of breast osteoblast-like cells in breast lesions with microcalcifications with respect to those without microcalcifications.

Results

In vitro data displayed that in the presence of calcium oxalate and activated monocytes, breast cancer cells undergo epithelial to mesenchymal transition. Also, in this condition, cells acquired an osteoblast phenotype, thus producing hydroxyapatite. To further confirm in vitro data, we studied 15 benign lesions with microcalcification from patients that developed a malignant condition in the same breast quadrant. Immunohistochemical analysis showed macrophages' polarization in benign lesions with calcium oxalate. Conclusions: Altogether, our data shed new light about the role of microcalcifications in breast cancer occurrence and progression.

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