Neuronal substance P drives metastasis through an extracellular RNA-TLR7 axis.

ABSTRACT: Tumour innervation is associated with worse patient outcomes in multiple cancers^1,2, which suggests that it may regulate metastasis. Here we observed that highly metastatic mouse mammary tumours acquired more innervation than did less-metastatic tumours. This enhanced innervation was driven by expression of the axon-guidance molecule SLIT2 in tumour vasculature. Breast cancer cells induced spontaneous calcium activity in sensory neurons and elicited release of the neuropeptide substance P (SP). Using three-dimensional co-cultures and in vivo models, we found that neuronal SP promoted breast tumour growth, invasion and metastasis. Moreover, patient tumours with elevated SP exhibited enhanced lymph node metastatic spread. SP acted on tumoral tachykinin receptors (TACR1) to drive d

SUBMITTER: Padmanaban V 

PROVIDER: S-EPMC11633843 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature