Breast Cancer Cell Lines AT-3 and E0771 Decrease Mechanical and Cold Sensitivity, Along With Oestrous Cycle and Inflammatory Marker Alterations, in Wild-Type C57BL/6J Female Mice.

Abstract

<h4>Background</h4>Breast cancer represents the most common cancer diagnosis and the leading cause of cancer-related death in women. Cancer is also associated with pain and changes in both tactile and temperature sensitivity that impair quality of life. While previous studies have investigated the effects of various chemotherapies in murine models of these symptoms, few have previously assessed the effects of cancer alone on these symptoms.<h4>Methods</h4>We evaluated the efficacy of murine AT-3 and E0771 breast cancer cell lines on the rate of tumour growth using the Von Frey test (mechanical sensitivity/allodynia) and the acetone test (cold sensitivity/allodynia) in female C57BL/6J wild-type mice. Evaluations for changes in oestrous cycle and mRNA expression in both tumour and whole brain tissue were then performed.<h4>Results</h4>While both cancer cell lines induced significant tumour growth, this growth was significantly greater in the AT-3 cell line than in the E0771 cell line. The AT-3 cell line significantly decreased mechanical and cold sensitivity (allodynia) and significantly altered the oestrous cycle to increase the time spent in a low oestrogen phase (oestrus). In comparison, the E0771 cell line significantly decreased mechanical and cold sensitivity (allodynia) without oestrous cycle alterations. When comparing gene expression in tumour tissue between the two cell lines, the E0771 cell line significantly increased expression of fatty acid amide hydrolase and calcitonin receptor-like.<h4>Conclusions</h4>These results demonstrate the significant impacts of breast cancer on mechanical and cold sensitivity and support the need for further investigations into possible interactions between cancer and chemotherapy in these modalities.<h4>Significance statement</h4>Cancer-associated pain and altered sensations significantly decrease patient quality of life. In our murine model, we have shown that breast cancer cell lines (AT-3 and E0771) alter mechanical and cold sensitivity. These changes coincided with oestrous cycle changes (AT-3) and mRNA expression changes (E0771). A better understanding of our findings will elucidate different mechanisms of action while identifying preventative strategies and potential interactions with chemotherapy.