Neuronal innervation of breast cancer promotes metastatic dissemination

Metastasis is a leading cause of mortality in breast cancer patients, yet the signaling promoting metastatic dissemination is not completely understood. Prior literature implicates neuronal innervation in tumor progression, including recent studies in breast cancer progression with the 4T1 and PyMT cell line orthotopic injection models. Our experiments address the immune limitations of these studies with an alternative model to elucidate neuronal control of metastatic breast cancer by using a MMTV-PyMT transplant model and resiniferatoxin (RTX) for denervation. To this end, we generated a robust array of spontaneous MMTV-PyMT tumors with various histological subtypes. These tumors were transplanted into RTX challenged MMTV-Cre mice. In contrast to previous literature, denervation did not impact survival or tumor growth. Interestingly, we noticed a slight reduction in the percent of the solid poorly differentiated tumors with a corresponding increase in tumors that contained a mixed pathology in RTX challenged mice. Strikingly, and consistent with prior work, we noted a reduction in metastasis with denervation. Together, these data suggest neuronal innervation promotes metastasis without impacting tumor growth.