Cancer stem cell and epithelial mesenchymal transition in chemoresistance of canine solid tumours

Abstract

There is increasing evidence for the presence of cancer stem cells in several solid tumors, and these cancer stem cells have a potential role in tumor initiation, aggression, and recurrence. Solid tumors occur frequently in dogs, where such tumors exhibit complexity when examined histologically. These tumors 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 the complexed histogenesis remains speculative, but cancer stem cells (CSCs) are likely involved. Canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelia to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Present investigation shows that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells can be induced to undergo EMT by transforming growth factor-β (TGF) and that these cells have an increased ability to form tumor sphere. CSCs possess self-renewing capacity, differentiation potential, high tumorigenicity in immunodeficient mice, and resistance to chemotherapy and radiation. Analysis of the characteristics of CSCs may contribute to the elucidation of the histogenesis underlying canine solid tumors, formulation of novel CSC-targeted therapeutic strategies, and development of biomarkers for early diagnostics and prognostic applications.