Feline mammary carcinomas display evidence of stemness, epithelial-mesenchymal plasticity, and metastasis-associated M2-like macrophage infiltration

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer-a consequence of high proliferation rates, stemness, epithelial-mesenchymal plasticity, and immune evasion. Feline mammary carcinomas (FMCs) are spontaneous mammary gland cancers associated with high rates of metastasis and death. The aggressive biological behavior of FMCs, as well as their lack of expression of hormone receptors, make FMCs an excellent naturally-occurring model of human triple-negative breast cancer (TNBC). Therefore, we investigated whether FMCs of increasing histologic grade (I-III) harbor characteristics comparable to human TNBC. We performed immunohistochemistry using markers of proliferation (Ki67), stemness (Sox2), and epithelial-mesenchymal plasticity (E-cadherin, vimentin). We found that FMCs expressed high levels of Sox2 and vimentin together with a grade-associated increase in Ki67 expression. Apart from these cancer cell-intrinsic properties, knowledge on the tumor microenvironment of FMCs is limited. To this end, we assessed the presence of T-cells (CD3), total macrophages (Iba1), and immunosuppressive M2-like macrophages (CD204) in FMCs. High-grade FMCs showed increased M2-like macrophage infiltration. Moreover, samples with evidence of vascular invasion and lymph node metastasis displayed increased total and M2-like macrophage infiltration. These findings suggest that the presence of intratumoral macrophages is associated with the biological aggressiveness and metastatic potential of FMCs. Taken together, our results support FMCs as a translational model of human TNBC.