Breast Tumor Microcalcification Induced by Bone Morphogenetic Protein-2: A New Murine Model for Human Breast Tumor Diagnosis

Widespread use of screening mammography has recently increased the detection of breast microcalcifications. ­ese nonpalpable microcalcifications with specific features in breast tissues are clinically considered an early indicator of breast carcinoma. Our goal in this study was to develop a murine breast microcalcification model for optimizing in vivo imaging. Recombinant human BMP-2 was expressed in E. coli, and the purified bioactive protein was used as inducing factor for the production of breast microcalcifications in a murine animal model. Syngeneic breast tumors were obtained by injection of MDA-MB-231 human breast cancer cells with Matrigel into the mammary fat pad of female nude mice. Difierent doses of bioactive rhBMP-2 were administered either as single or multiple intraperitoneal injections or directly into tumor on a weekly basis. ­ree weeks after the first injection of rhBMP-2, the microcalcification of breast tumor was detected by microcomputed tomography followed by intravenous injection of radiotracer [18F] Sodium uoride for positron emission tomography imaging. Our findings indicate that rhBMP-2 induced microcalcifications of breast tumor by both systemic and direct injection of rhBMP-2 into tumors in a dose-dependent manner. Although little is known about the molecular mechanism of microcalcification, here we report a new murine model of human breast tumor induced microcalcification by rhBMP-2 to optimize in vivo imaging methods and to study the role of BMP-2 as a mediator of pathological mineralization and bone-like microcalcification formation in breast tumor. ­is BMP-2-induced microcalcification model may allow us to discriminate the type of microcalcification in tumors and to perform quantitative analysis on the calcification as a new detection strategy for early identification of pathological mineralization of breast tissues in women.