Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth
Antonio Barbieri
Animal Facility, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorGiuseppe Palma
Animal Facility, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorAldo Giudice
Animal Facility, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorAntonella Petrillo
Radiology Section, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorMario Petrillo
Radiology Section, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorSabrina Bimonte
Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy
Search for more papers by this authorMaria Di Benedetto
Department of Experimental and Clinical Medicine, University ‘Federico II’, Naples, Italy
Search for more papers by this authorGiuseppe Esposito
Endocrinology Section, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorPaola Stiuso
Department of Biochemistry and Biophysics Second University of Naples, Naples, Italy
Search for more papers by this authorCorresponding Author
Alberto Abbruzzese
Department of Biochemistry and Biophysics Second University of Naples, Naples, Italy
Michele CARAGLIA, M.D., Ph.D., Alberto ABBRUZZESE, Ph.D., Department of Biochemistry and Biophysics, Second University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy. Tel.: +39-0815665871 Fax: +39-0815665863 E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Michele Caraglia
Department of Biochemistry and Biophysics Second University of Naples, Naples, Italy
Michele CARAGLIA, M.D., Ph.D., Alberto ABBRUZZESE, Ph.D., Department of Biochemistry and Biophysics, Second University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy. Tel.: +39-0815665871 Fax: +39-0815665863 E-mail: [email protected], [email protected]Search for more papers by this authorClaudio Arra
Animal Facility, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorAntonio Barbieri
Animal Facility, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorGiuseppe Palma
Animal Facility, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorAldo Giudice
Animal Facility, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorAntonella Petrillo
Radiology Section, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorMario Petrillo
Radiology Section, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorSabrina Bimonte
Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy
Search for more papers by this authorMaria Di Benedetto
Department of Experimental and Clinical Medicine, University ‘Federico II’, Naples, Italy
Search for more papers by this authorGiuseppe Esposito
Endocrinology Section, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorPaola Stiuso
Department of Biochemistry and Biophysics Second University of Naples, Naples, Italy
Search for more papers by this authorCorresponding Author
Alberto Abbruzzese
Department of Biochemistry and Biophysics Second University of Naples, Naples, Italy
Michele CARAGLIA, M.D., Ph.D., Alberto ABBRUZZESE, Ph.D., Department of Biochemistry and Biophysics, Second University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy. Tel.: +39-0815665871 Fax: +39-0815665863 E-mail: [email protected], [email protected]Search for more papers by this authorCorresponding Author
Michele Caraglia
Department of Biochemistry and Biophysics Second University of Naples, Naples, Italy
Michele CARAGLIA, M.D., Ph.D., Alberto ABBRUZZESE, Ph.D., Department of Biochemistry and Biophysics, Second University of Naples, Via Costantinopoli, 16, 80138 Naples, Italy. Tel.: +39-0815665871 Fax: +39-0815665863 E-mail: [email protected], [email protected]Search for more papers by this authorClaudio Arra
Animal Facility, National Institute of Tumours ‘G. Pascale’, Naples, Italy
Search for more papers by this authorAbstract
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.
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