Understanding of tumourigenesis in canine mammary tumours based on cancer stem cell research.

Mammary tumours occur frequently in female dogs, where such tumours exhibit complexity when examined histologically. These tumours are composed not only of proliferative luminal epithelial cells, but also of myoepithelial cells and/or mesenchymal cells with cartilage and osseous tissues in a solitary mass. The origin of this complexed histogenesis remains speculative, but cancer stem cells (CSCs) are likely involved. CSCs possess self-renewing capacity, differentiation potential, high tumourigenicity in immunodeficient mice, and resistance to chemotherapy and radiation. These cells are at the apex of a hierarchy in cancer tissues and are involved in tumour initiation, recurrence, and metastasis. For these reasons, understanding the properties of CSCs is of paramount importance. Analysis of the characteristics of CSCs may contribute to the elucidation of the histogenesis underlying canine mammary tumours, formulation of novel CSC-targeted therapeutic strategies, and development of biomarkers for early diagnostic and prognostic applications. Here, we review research on CSCs in canine mammary tumours, focusing on: (1) identification and properties of CSCs; (2) hypotheses regarding hierarchal structures in simple type, complex type and mixed tumours of the canine mammary gland; and (3) current and prospective studies of CSC metabolism.