Mechanism Linking Aggression Stress through Inflammation to Cancer

Clinical studies indicates that stress increases the immune cell apoptosis, decreases the spleen and thymus cell content, similarly the natural killer (NK) activity in the spleen, and it compromises the antitumor immune response in mice [1]. Examples of stressors associated with alterations in the autonomic nervous system (ANS) and in the hypothalamic-pituitary-adrenal (HPA) axis include aggression and post-traumatic stress disorder (PTSD) [2,3]. It can lead to chronic alterations in neuroendocrine dynamics and also alter multiple physiological processes involved in tumor pathogenesis [4,5]. Complex cell interactions in the tumor and its microenvironment play an important role in tumorigenesis and cancer progression. Cooperation between oncogenic genetic lesions is required for tumor development. Interaction between RasV12 and scribble involves JNK signaling propagations and JNK-induced upregulation of JAK/ STAT-activating cytokines, a compensatory growth mechanism for tissue damage, a stress condition that activates JNK signaling. Similar cooperative mechanisms play a role in the development of other human cancers [6]. Stress events suppress a broad spectrum of immunological responses. The stress decreased the potential of the spleen cells to turn into antitumor cytotoxic T lymphocytes (CTLs) after in vitro restimulation. Stress significantly impairs the antitumor T cell responses through its suppressive effect on Th1-type CD4+ T cells. [7,8]. Social confrontation, aggression and hypothermia resulted in increased (lung) metastasis from injected breast cancer cells [9]. Swim stress and social confrontation caused a 2-to 5-fold increase in the number of rat MADB106 breast tumor metastases in lung. Cellular and molecular events that promote cancer growth are also affected by stress: might compromise DNA repair mechanisms. Stress can also influence the expression of viral oncogenes and replication of tumorigenic viruses [10]. Tumor production of vascular endothelial growth factor (VEGF), indicate that stress might promote tumor growth by facilitating development of blood supply [11]. VEGF also interferes with the development of T cells and the functional maturation of dendritic cells, with possible effects on anti-tumor immune responses [12]. Materials and Methods