To study the ectopic chondrogenesis in canine mammary mixed
tumors, the expression of bone morphogenetic protein-6 (BMP-6) and specific
BMP receptors (BMPRs), BMPR-IA, BMPR-IB, and BMPR-II, was examined using immunohistochemical and immunoblot analysis in 39 canine mammary gland
tumors. Immunohistochemically,
BMP-6 and all three types of BMPRs were coexpressed in the myoepithelial cells and chondrocytes in six of eight benign mixed
tumors. In complex
adenomas, myoepithelial cells showed an expression pattern of
BMP-6, BMPR-IA, and BMPR-II similar to those in benign mixed
tumors, whereas immunoreactivity for BMPR-IB was very mild. The myoepithelial cells proliferating within the basement membrane showed more intense immunoreactivity for
BMP-6 and all BMPRs as compared with those proliferating in the interstitial areas. Western blotting analysis revealed immunopositive bands at 40-45 kDa for
BMP-6 in the samples from simple and complex
adenomas and benign mixed
tumors. The BMPR-IB-specific bands at 45 kDa were most detected in benign mixed
tumors. Because among BMPRs, BMPR-IB is thought to be the major receptor for
BMP-6 for primary chondrogenesis, these findings suggest that the expression of BMP and its receptors on the myoepithelial cells might play a role in the ectopic cartilage formation in canine mammary gland
tumors, especially in benign mixed
tumors.