Co-localization of Chondromodulin-I (ChM-I) and Bone Morphogenetic Protein-6 (BMP-6) in Myoepithelial Cells of Canine Mammary Tumors

Abstract

ABSTRACT. To compare the roles of chondromodulin-I (ChM-I) and bone morphogenetic protein-6 (BMP-6) in ectopic mesenchymal tissue formation in canine mammary gland tumors, 33 tumors and 2 normal mammary glands were examined. Immunohistochemical analysis revealed co-expression of ChM-I and BMP-6 in canine mammary tumors. In mixed tumors, newly formed woven bone with ossified cartilage matrix was observed in 4/9 cases. The osteoblasts lining the woven bone showed moderate immunoreactivity to ChM-I and BMP-6. Almost all chondrocytes and proliferative myoepithelial cells within the basement membrane showed intense immunoreactivity to both, and the myoepithelial cells adjacent to the mature cartilage showed the most intense immunoreactivity. The immunoreactivity to ChM-I and BMP-6 of the interstitial myoepithelial cells in the myxomatous stroma varied in each focus of mixed tumors. Similar findings were found in complex adenomas. In simple adenomas, hyperplasic myoepithelial cells within the basement membrane showed moderate immunoreactivity to both markers. Western blot analysis detected a 25 kDa band of ChM-I in fresh tissue samples from three mixed tumors. Our results support the hypothesis that proliferating myoepithelial cells with ChM-I and BMP-6 expression play important roles in mesenchymal metaplasia in canine mammary tumors.

Development, Anatomy, Histology, Lymphatic Drainage, Clinical Features, and Cell Differentiation Markers of Canine Mammary Gland Neoplasms

“…7,20,24,28,31,36,72,91 This shift in the myoepithelial immunoprofile was associated with an increased expression of bone morphogenetic protein-6 and chondromodulin-I, proteins that may be involved in ectopic cartilage and bone formation. 40,91 However, we do not know the role of the stromal connective tissue, such as interstitial myofibroblasts or fibroblasts in mesenchymal tissue formation, and how these cells might interact with the myoepithelial cells to produce the connective tissue. 91 In humans, where the majority of breast malignancies are composed of a single population of epithelial cells (corresponding to simple tumors in dogs), most of the antibodies against basal cell markers are also able to identify the preexisting myoepithelial cell layer.…”

Canine Mammary Mixed Tumours: A Review

“…Calponin [29], β II tubulin [46], versican and aggrecan [34, 35], collagens [34, 47, 48], 3B3(-) neoepitope [33], bone morphogenetic protein 6 and its receptors (BMP-6) [49–51], and chondromodulin-1 (ChM-1) [51] are expressed in myoepithelial proliferation areas and/or chondrocytes and seem to participate in cartilage formation. Molecules involved in cell-extracellular matrix adhesion, such as tenascin, fibronectin, and the neural cell adhesion molecule (NCAM), apparently contribute to the differentiation of the myoepithelium [52].…”

Mammary Tumours in Dogs and its Treatment Option- A Review

“…In canine mammary tumors, the TNM classification separates tumors, where T relates to tumor size and whether it has invaded nearby tissue, N describes the involvement of regional lymph nodes and M describes metastasis. In a survey of 54 cases, two-year survival percentages were 62% for T1 tumors and 23% for T2 and T3 tumors [41,[51][52][53].…”