Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth.

""Accumulating evidence suggest that chronic stress can be a cofactor for the initiation and progression of cancer. Here we evaluated the role of endothelial nitric oxide synthase (eNOS) in stress-promoted tumor growth of murine B16F10 melanoma cell line in C57BL\\\/6 mice. Animals subjected to restraint stress showed increased levels ACTH, enlarged adrenal glands, reduced thymus weight and a 3.61 fold increase in tumor growth in respect to no-stressed animals. Tumor growth was significantly reduced in mice treated with the beta antagonist propranolol. Tumor samples obtained from stressed mice displayed high levels of VEGF protein in immunohistochemistry (IHC). Since VEGF can induce eNOS increase, and NO is a relevant factor in angiogenesis, we assessed the levels of eNOS protein by western blot analysis. We found a significant increase in eNOS levels in tumor samples from stressed mice, indicating an involvement of this enzyme in stress-induced tumor growth. Accordingly, chronic stress did not promote tumor growth in eNOS-\\\/- mice. These results disclose for the first time a pivotal role for eNOS in chronic stress-induced initiation and promotion of tumor growth.. . "