Stress hormones concentrations in the normal microenvironment predict risk for chemically induced cancer in rats

Abstract

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.

Circulating catecholamines are associated with biobehavioral factors and anxiety symptoms in head and neck cancer patients

“…In a previous study using an oral carcinogenesis model in rats, we demonstrated that increased pre-carcinogen NE concentrations in the normal tissue microenvironment were predictive for oral SCC occurrence, as well as lower expression of the tumor-suppressor gene pCDKN2a-p16. In addition, higher levels of NE in the tumor microenvironment were associated with lower immune response [ 53 ]. The presence of β-adrenergic receptors for NE and E has also been identified in HNSCC cell lines [ 18 , 54 ].…”

Psychological Stress and Cellular Aging in Cancer: A Meta-Analysis

“…OS has been shown to play an important role in tumor initiation, promotion, and progression [67, 68] and is implicated in the pathogenesis of various biological systems and organs (reviewed lately by Kruk et al [77]). The role of PS in increased DNA damage has been supported by human studies, in vitro studies with animals, and cell lines exposed to stress hormones [14, 59, 113]. These multivariate complexities show the difficulty in determining and expressing the association between PS and cancer risk.…”

Genetic variants in SLC22A3 contribute to the susceptibility to colorectal cancer

“…Many studies have indicated that stress hormones were associated with cancer risk and progression, and SLC22A3 was associated with the transportation and reuptake of norepinephrine . The group of youngers or men may suffer a more stressful life due to various kinds of pressure from family or the society, where norepinephrine would be more generated.…”