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 observed in such foci. The calcium phosphate is a physiologic component of bones and teeth. Since the expression of messenger (m) RNAs of osteopontin (OPN), osteocalcin (OC), osteonectin (ON), and matrix gla protein (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 observed in human breast cancers.

EXPERIMENTAL DESIGN

Cell types expressing mRNAs of OPN, ON or MGP were identified with combination of in situ hybridization and immunohistochemistry.

RESULTS

The OPN mRNA-expressing 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 staining the adjacent section with the anti-CD68 PG-M1 monoclonal antibody which specifically recognizes macrophages. Neither ON mRNA-expressing cells nor MGP mRNA-expressing cells appeared to correlate with the deposition of calcium phosphate.

CONCLUSIONS

The OPN protein produced by macrophages appeared to play a significant role for development of calcifying foci within necrotic area of breast cancers.