Hirota S, Ito A, Nagoshi J, Takeda M, Kurata A, Takatsuka Y, Kohri K, Nomura S, Kitamura Y
Department of Pathology, Osaka University Medical School, Suita, Japan.
Lab Invest. 1995 Jan;72(1):64-9.
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.
Cell types expressing mRNAs of OPN, ON or MGP were identified with combination of in situ hybridization and immunohistochemistry.
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.
The OPN protein produced by macrophages appeared to play a significant role for development of calcifying foci within necrotic area of breast cancers.
钙化灶的形成是人类乳腺癌中相当常见的现象，在这些病灶中可观察到磷酸钙的沉积。磷酸钙是骨骼和牙齿的生理成分。由于骨桥蛋白（OPN）、骨钙素（OC）、骨连接蛋白（ON）和基质Gla蛋白（MGP）的信使核糖核酸（mRNA）在骨骼和牙齿中已有表达描述，我们检测了人类乳腺癌中观察到的钙化灶中OPN、OC、ON或MGP的mRNA表达情况。
通过原位杂交和免疫组化相结合的方法鉴定表达OPN、ON或MGP mRNA的细胞类型。
表达OPN mRNA的细胞聚集在癌细胞巢内的坏死灶周围，用抗OPN抗体检测发现OPN蛋白定位于磷酸钙沉积的坏死灶中。用特异性识别巨噬细胞的抗CD68 PG-M1单克隆抗体对相邻切片染色，将表达OPN mRNA的细胞鉴定为巨噬细胞。表达ON mRNA的细胞和表达MGP mRNA的细胞似乎都与磷酸钙的沉积无关。
巨噬细胞产生的OPN蛋白似乎在乳腺癌坏死区域钙化灶的形成中起重要作用。
