EXPRESSION OF BONE-MATRIX PROTEIN MESSENGER RIBONUCLEIC-ACIDS IN HUMAN BREAST CANCERS - POSSIBLE INVOLVEMENT OF OSTEOPONTIN IN DEVELOPMENT OF CALCIFYING FOCI

BACKGROUND: Development of calcifying foci is a fairly common finding in human breast cancers, and the deposition of calcium phosphate is ob served in such foci. The calcium phosphate is a physiologic component of bones and teeth. Since the expression of messenger (m) RNAs of oste opontin (OPN), osteocalcin (OC), osteonectin (ON), and matrix gla prot ein (MGP) has been described in bones and teeth, we examined the mRNA expression of OPN, OC, ON, or MGP in the calcifying foci that were obs erved in human breast cancers. EXPERIMENTAL DESIGN: Cell types express ing mRNAs of OPN, ON or MGP were identified with combination of in sit u hybridization and immunohistochemistry. RESULTS: The OPN mRNA-expres sing cells clustered around the necrotic foci within cancer cell nests , and the examination with anti-OPN antibody revealed that OPN protein was localized in such necrotic foci where calcium phosphate deposited . The OPN mRNA-expressing cells were identified as macrophages by stai ning the adjacent section with the anti-CD68 PC-M1 monoclonal antibody which specifically recognizes macrophages. Neither ON mRNA-expressing cells nor MGP mRNA-expressing cells appeared to correlate with the de position of calcium phosphate. CONCLUSIONS: The OPN protein produced b y macrophages appeared to play a significant role for development of c alcifying foci within necrotic area of breast cancers.