Open AccessRole of endothelial nitric oxide synthase (eNOS) in chronic stress‐promoted tumour growth
Author(s) -
Barbieri Antonio,
Palma Giuseppe,
Rosati Alessandra,
Giudice Aldo,
Falco Antonia,
Petrillo Antonella,
Petrillo Mario,
Bimonte Sabrina,
Benedetto Maria Di,
Esposito Giuseppe,
Stiuso Paola,
Abbruzzese Alberto,
Caraglia Michele,
Arra Claudio
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01375.x
Subject(s) - enos , endocrinology , medicine , nitric oxide synthase , angiogenesis , vascular endothelial growth factor , nitric oxide , chronic stress , biology , vegf receptors
Accumulating evidence suggests 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 tumour growth of murine B16F10 melanoma cell line in C57BL/6 mice. Animals subjected to restraint stress showed increased levels adrenocorticotropic hormone, enlarged adrenal glands, reduced thymus weight and a 3.61‐fold increase in tumour growth in respect to no‐stressed animals. Tumour growth was significantly reduced in mice treated with the β‐antagonist propranolol. Tumour samples obtained from stressed mice displayed high levels of vascular endothelial growth factor (VEGF) protein in immunohistochemistry. Because VEGF can induce eNOS increase, and nitric oxide 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 tumour samples from stressed mice, indicating an involvement of this enzyme in stress‐induced tumour growth. Accordingly, chronic stress did not promote tumour growth in eNOS −/− mice. These results disclose for the first time a pivotal role for eNOS in chronic stress‐induced initiation and promotion of tumour growth.