TY - JOUR
T1 - Stress hormones concentrations in the normal microenvironment predict risk for chemically induced cancer in rats
AU - Valente, Vitor Bonetti
AU - Verza, Flávia Alves
AU - Lopes, Felipe Yudi Kabeya
AU - Ferreira, Joana Zafalon
AU - dos Santos, Paulo Sérgio Patto
AU - Sundefeld, Maria Lúcia Marçal Mazza
AU - Biasoli, Éder Ricardo
AU - Miyahara, Glauco Issamu
AU - Soubhia, Ana Maria Pires
AU - de Andrade, Mariza
AU - de Oliveira, Sandra Helena Penha
AU - Bernabé, Daniel Galera
N1 - Funding Information:
This study was supported by the research foundation Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES/DS ; the Psychoneuroimmunology Research Center , Oral Oncology Center , Department of Pathology and Clinical Propedeutics , Department of Basic Sciences (Araçatuba Dental School, São Paulo State University - Unesp) ; and the Department of Animal Clinic, Surgery and Reproduction (Araçatuba Veterinary Medicine School, São Paulo State University - Unesp) .
Funding Information:
This study was supported by the research foundation Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES/DS; the Psychoneuroimmunology Research Center, Oral Oncology Center, Department of Pathology and Clinical Propedeutics, Department of Basic Sciences (Ara?atuba Dental School, S?o Paulo State University - Unesp); and the Department of Animal Clinic, Surgery and Reproduction (Ara?atuba Veterinary Medicine School, S?o Paulo State University - Unesp).
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/3
Y1 - 2018/3
N2 - Evidence show that stress hormones can influence cancer progression, but its role in carcinogenesis is poorly understood. In this study, we used a new method based on oral carcinogenesis model in rats to test the hypothesis that physiological levels of stress hormones in the normal tissue microenvironment would have significant predictive value for chemically induced cancer occurrence. Male Wistar rats were submitted to a tongue biopsy for measuring not-stress induced levels of norepinephrine, corticosterone, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) in the tissue before carcinogenic induction. Rats were treated with the 4-nitroquinoline-1-oxide (4NQO) chemical carcinogen for twenty weeks and then euthanized for microscopic evaluation of the tongue lesions. Increased pre-carcinogen norepinephrine concentrations and reduced basal corticosterone levels in the normal tissue microenvironment were predictive for oral squamous cell carcinoma (OSCC) occurrence. Likewise, increased pre-carcinogen norepinephrine levels in the normal microenvironment were associated a lower expression of pCDKN2a-p16 in OSCCs. Post-carcinogen levels of corticosterone and BDNF in oral leukoplakia tissues (precursor lesion of OSCC) and post-carcinogen corticosterone concentrations in OSCCs were higher than basal levels in the normal mucosa. Increased norepinephrine concentrations in OSCCs were associated to a greater tumor volume and thickness. Furthermore, higher levels of norepinephrine, ACTH and BDNF in OSCCs were associated to a lesser intensity of the lymphoplasmocytic infiltrate. This study shows that pre-carcinogen stress hormones levels in the normal microenvironment may be predictive for chemically induced cancer in rats. Moreover, chemical carcinogenesis can promote stressor-like effects with hormonal changes in the tissue microenvironment, which may be associated to tumor progression.
AB - Evidence show that stress hormones can influence cancer progression, but its role in carcinogenesis is poorly understood. In this study, we used a new method based on oral carcinogenesis model in rats to test the hypothesis that physiological levels of stress hormones in the normal tissue microenvironment would have significant predictive value for chemically induced cancer occurrence. Male Wistar rats were submitted to a tongue biopsy for measuring not-stress induced levels of norepinephrine, corticosterone, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) in the tissue before carcinogenic induction. Rats were treated with the 4-nitroquinoline-1-oxide (4NQO) chemical carcinogen for twenty weeks and then euthanized for microscopic evaluation of the tongue lesions. Increased pre-carcinogen norepinephrine concentrations and reduced basal corticosterone levels in the normal tissue microenvironment were predictive for oral squamous cell carcinoma (OSCC) occurrence. Likewise, increased pre-carcinogen norepinephrine levels in the normal microenvironment were associated a lower expression of pCDKN2a-p16 in OSCCs. Post-carcinogen levels of corticosterone and BDNF in oral leukoplakia tissues (precursor lesion of OSCC) and post-carcinogen corticosterone concentrations in OSCCs were higher than basal levels in the normal mucosa. Increased norepinephrine concentrations in OSCCs were associated to a greater tumor volume and thickness. Furthermore, higher levels of norepinephrine, ACTH and BDNF in OSCCs were associated to a lesser intensity of the lymphoplasmocytic infiltrate. This study shows that pre-carcinogen stress hormones levels in the normal microenvironment may be predictive for chemically induced cancer in rats. Moreover, chemical carcinogenesis can promote stressor-like effects with hormonal changes in the tissue microenvironment, which may be associated to tumor progression.
KW - BDNF
KW - Cancer
KW - Carcinogenesis
KW - Oral cancer
KW - Stress hormones
UR - http://www.scopus.com/inward/record.url?scp=85033785940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85033785940&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2017.11.001
DO - 10.1016/j.psyneuen.2017.11.001
M3 - Article
C2 - 29150404
AN - SCOPUS:85033785940
SN - 0306-4530
VL - 89
SP - 229
EP - 238
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
ER -