Cartilage Formation as a Differentiation Route of Myoepithelial Cells in Canine Mammary Tumours: Involvement of Myofibroblasts?

Abstract

In canine mammary tumours the presence of large areas of spindle cells with myxoid differentiation (so‐called complex mammary tumours) or areas with cartilage and bone (mixed mammary tumours) is a frequent finding. In most cases these tumours are benign. It has been suggested that this route of differentiation may be a tumor suppressor route and this warrants a closer investigation of this route in canine mammary mixed tumours. The origin of the cartilage is supposed to be the myoepithelial cell which may have undergone an epithelial to mesenchymal transition. In this study we concentrated on the composition of the extracellular matrix (ECM) in the stroma of these tumours because this may shed light on the phenotypes of the different cells involved. The immunohistochemical expression of ECM components (aggrecan, versican, collagen II, link protein, 3B3/chondroitin sulphate‐6 epitope) of the tumor stroma indicates a close relationship between the myxoid spindle cells in complex and mixed tumours and the precartilageneous and cartilage tissues in mixed tumors. Semiquantitative PCR analyses of different types of normal tissue and tumours showed, next to a rather general expression of versican, expression of aggrecan and collagen type II in complex and mixed tumours (as expected because they are (pre)cartilage components) and in epitheliomas, but also of collagen type II in simple (i.e., noncomplex) tumors and, although faintly, in normal glands. Staining of cytoskeletal proteins in the spindle cells of complex tumors demonstrates expression of cytokeratin 14, α‐smooth muscle actin and vimentin in these cells, raising the possibility that they may be modified myofibroblasts. We hypothesize that myofibroblasts in the tumor stroma may be the precursors of cartilage and that in the stroma of normal glands they may differentiate into myoepithelial cells.