Characterisation of a Mouse Model of Breast Cancer with Metabolic Syndrome

Background/Aim: Patients with breast cancer and metabolic syndrome have poorer outcomes. We aimed to develop and characterise an apolipoprotein E-null/aromatase knockout (ApoE(-/-)ArKO) mouse model of breast cancer with metabolic syndrome to aid research of the mechanisms behind poor prognosis. Materials and Methods: Wild-type, ApoE(-/-) and ApoE(-/-)ArKO mice were orthotopically implanted with EO771 murine breast cancer cells. Tumour growth was monitored and tumours investigated for pathological features such as cancer-associated adipocytes, hypoxia and cancer cell proliferation. Results: Tumours from ApoE(-/-)ArKO mice were significantly more proliferative than those from wild-type mice (p=0.003), and exhibited reduced expression of insulinlike growth factor binding protein-5 (p=0.002). However, ApoE(-/-)ArKO mice also had a reduced rate of metastasis compared to wild-type and ApoE(-/-) mice. Tumour hypoxia and the number of cancer-associated adipocytes did not differ. Conclusion: The ApoE(-/-)ArKO model with E0771 breast cancer provides a novel mouse model to investigate the effects of metabolic syndrome on aspects of breast tumour biology.