Vagotomy Enhances Experimental Metastases of 4THMPC Breast Cancer Cells and Alters Substance P Level

We have previously demonstrated that inactivation of capsaicin-sensitive sensory neurons enhances lung and heart metastases of breast carcinoma. Because a significant part of sensory innervation of lung tissue is supplied by the vagus nerve, we here examined the effects of unilateral mid-cervical vagotomy in the metastases of 4THMpc breast carcinoma and tissue Substance P (SP) levels. Balb-c mice were injected orthotopically with 4THMpc cells 1 week after vagotomy. Animals were sacrificed 27-30 days after injection of 4THMpc cells and the extent of metastases was determined. Unilateral vagotomy, right or left significantly increased the lung, liver and kidney metastases without altering the growth rate of the primary tumor. Heart metastases were increased only following left vagotomy. The changes in SP levels were somewhat surprising such that vagotomy actually increased while sham-operation decreased SP levels in lung. The effect of sham-operation was reversed by unilateral vagotomy demonstrating that vagal activity decreases total SP levels in the lung. Increased SP levels might be due to decreased degradation of the peptide. Presence of the tumor markedly increased SP level in the lung, which was more prominent in vagotomized animals. These results provide evidence that vagal activity may protect against metastatic disease. © 2008 Elsevier B.V. All rights reserved