Relations between different coping strategies for social stress, tumor development and neuroendocrine and immune activity in male mice

Azpı́roz, Arantza; Miguel, Zurine De; Fano, Eduardo; Vegas, Oscar

doi:10.1016/j.bbi.2007.10.007

Cited by 47 publications

(38 citation statements)

References 51 publications

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“…10 This seems to be true also for melanoma at least in in vivo models. 32,33 Our work provides evidence that stress hormones like NE and E can significantly stimulate the malignancy of melanoma cells at various levels and that b-ARs, likely involved in this response, are largely expressed in melanoma cell lines and cutaneous melanomas. It is the first time, to our knowledge, that b-ARs are demonstrated in a large series of human cutaneous melanocytic lesions, and even in melanocytic naevi, suggesting a potential influence of catecholamines also in benign counterparts.…”

Section: Discussionmentioning

confidence: 74%

β-adrenoceptors are upregulated in human melanoma and their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell lines

Moretti

Massi

Farini

et al. 2013

Laboratory Investigation

112

108

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Recent studies sight b-adrenergic receptor (AR) antagonists as novel therapeutic agents for melanoma, as they may reduce disease progression. Here within, we evaluated the expression of b-ARs in a series of human cutaneous melanocytic lesions, and studied the effect of their endogenous agonists, norepinephrine (NE) and epinephrine (E), on primary and metastatic human melanoma cell lines. Using immunohistochemistry, we found that both b1-and b2-ARs are expressed in tissues from benign melanocytic naevi, atypical naevi and malignant melanomas and that expression was significantly higher in malignant tumours. Melanoma cell lines (human A375 primary melanoma cell line and human Hs29-4T metastatic melanoma cell lines) also expressed b1-and b2-ARs by measuring transcripts and proteins. NE or E increased metalloprotease-dependent motility, released interleukin-6 and 8 (IL-6, IL-8) and vascular endothelial growth factor (VEGF). These effects of catecholamines were inhibited by the unselective b-AR antagonist propranolol. The role of soluble factors elicited by catecholamines seemed pleiotropic as VEGF synergized with NE increased melanoma invasiveness through 3D barriers, while IL-6 participated in stromal fibroblast activation towards a myofibroblastic phenotype. Our results indicate that NE and E produce in vitro via b-ARs activation a number of biological responses that may exert a pro-tumorigenic effect in melanoma cell lines. The observation that b-ARs are upregulated in malignant melanoma tissues support the hypothesis that circulating catecholamines NE and E, by activating their receptors, favour melanoma progression in vivo. Melanoma represents the most aggressive type of skin cancer, with an increasing incidence found especially in young adults. A significant reduction in mortality has been not observed, despite a noteworthy improvement in early diagnosis achieved in recent years. 1 At present, no medical option can cure metastatic melanoma (MM) and the only effective treatment for the eradication of the disease is early-phase surgery. 2 Hence, increased knowledge of the biological pathways underlying the process of melanoma dissemination and metastasis is crucial in order to identify new therapeutic targets.Previous studies have shown that various human solid tumours, such as breast, colon, prostatic, ovary, nasopharyngeal and oral cancer, express b2-adrenoceptor (b2-AR), raising the possibility that such receptors may affect invasion and dissemination processes. [3][4][5][6][7][8] Moreover, some stress neurotransmitters, such as norepinephrine (NE) and epinephrine (E), have been demonstrated to contribute to the regulation of tumour cell invasion, at least in part through b-AR activation. 6,7,9 Interactions between tumour cells and soluble factors originated from the nervous system has recently been proposed to favour metastasis formation. 10 Improved survival rates have been demonstrated in mice with metastatic tumour by combined administration of b-AR antagonists. 11 In addition, recent evidence suggests a ...

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Section: Discussionmentioning

confidence: 74%

β-adrenoceptors are upregulated in human melanoma and their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell lines

Moretti

Massi

Farini

et al. 2013

Laboratory Investigation

112

108

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“…Recent evidence has also shown that decidual NK (dNK) cells play a key role in controlling trophoblast invasion and vascular remodeling (33,34). Although NK cells are an important cell type within the innate immune system and also act as sentinel cells in other models (35)(36)(37), their exact function at the maternal-fetal interface remains incompletely defined. Recent studies have reported that CD27, which belongs to the TNF receptor family, is an important marker in distinguishing different subsets of NK cells (38,39).…”

mentioning

confidence: 99%

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface

Sun

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

257

218

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Natural killer (NK) cells accumulate at the maternal-fetal interface in large numbers, but their exact roles in successful pregnancy remain poorly defined. Here, we provide evidence that T H 17 cells and local inflammation can occur at the maternal-fetal interface during natural allogenic pregnancies. We found that decidual NK cells promote immune tolerance and successful pregnancy by dampening inflammatory T H 17 cells via IFN-γ secreted by the CD56 bright CD27 + NK subset. This NK-cell-mediated regulatory response is lost in patients who experience recurrent spontaneous abortions, which results in a prominent T H 17 response and extensive local inflammation. This local inflammatory response further affects the regulatory function of NK cells, leading to the eventual loss of maternal-fetal tolerance. Thus, our data identify NK cells as key regulatory cells at the maternal-fetal interface by suppressing T H 17-mediated local inflammation.regulatory NK cells | fetomaternal tolerance D uring pregnancy, allogeneic fetal cells invade the maternal decidua but they are protected from the maternal immune system. This invasion of extraembryonic trophoblasts does not harm gestation during normal pregnancy; it establishes tolerance at the maternal-fetal interface (1), (2), although the mechanism of such tolerance is not clear. In addition, inflammatory responses induced by a variety of mechanisms can result in embryo loss, but mild inflammation can be effectively controlled through regulatory mechanisms to maintain successful pregnancy (3). Thus, suppression of strong inflammatory responses is essential to ensure normal pregnancy (4, 5), although the mechanisms involved in regulating local inflammation without compromising overall maternal immunity during a successful pregnancy remain unknown.Multiple mechanisms are potentially involved in promoting immune tolerance during pregnancy. For example, T H 2 cytokine polarization (6-9), the expression of the Fas ligand on trophoblast cells (10), and the inhibition of complement activation (11) are crucial for ensuring tolerance at the maternal-fetal interface. In addition, a delicate balance exists between inhibitory (PD-L1, Stat3, and TGF-β1) and stimulatory (CD80 and CD86) signals during the establishment of immune privilege (12-18). Furthermore, studies have shown that galectin-1 (19) and indoleamine 2,3-dioxygenase (20) play pivotal roles in maternal-fetal tolerance. Several types of immune cells, such as CD4 + CD25 + regulatory T cells, are also essential in the generation of maternal-fetal tolerance in mice and humans (7,(21)(22)(23)(24). Furthermore, natural killer (NK) T cells and immature dendritic cells have been reported to promote the expansion of Treg cells that confer protection of the fetus (19).Despite considerable progress, many questions remain unanswered. The most striking feature at the maternal-fetal interface is the accumulation of NK cells, which account for ∼60-90% of immune cells in the decidua in humans during early pregnancy (25)(26)(27)(28)(29) and a...

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“…15,32 Several animal experiments have demonstrated that chronic stress conditions or social defeat lead to increased HPA activity, decreased NK-cell function and increased melanoma metastasis. [33][34][35] Studies in nonskin tumours suggest that psychosocial factors such as stress, depression or lack of social support have an influence on the progression of tumours. For example, Price et al 36 showed that a combination of low social support, followed by exposure to extreme stress, leads to a ninefold increase in breast cancer incidence, an interaction that may be influenced by spouse coping strategies.…”

Section: Neuroendocrine-immune Interaction and Skin Cancer Control: Tmentioning

confidence: 99%

Psychological support of skin cancer patients

Peters

2012

British Journal of Dermatology

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SummaryThe diagnosis of skin cancer imposes a great stress on our patients. Ultraviolet (UV) radiation-induced skin cancers are on the rise and frequently occur in younger patients and unexposed sites despite improved protective behaviour. Environmental factors and lifestyle habits have changed greatly in the last century and in addition to UV radiation exposure, psychosocial stressors and physical inactivity may play a role in the rising tumour incidence. With environmental stressors such as UV radiation they share the capacity to change the stress reaction. So far research into the interaction between stress, cancer and psychosocial intervention has generated some interesting results with respect to improvement of quality of life and the function of the hypothalamic-pituitary-adrenal axis, the sympathetic axis and natural killer cells. These results hint at a suppressive effect of chronic stress on cellular immunity and the importance of a sufficient length and intensity of any psychosocial intervention for it to be effective. Nevertheless, the evidence remains inconclusive and does not take into account the findings of current psychoneuroimmunological research. This research has demonstrated the importance of a third stress axis along which neurotrophins and neuropeptides are effective. Along this axis, regulatory mechanisms may contribute to suppress tumoricidal immune responses. This may be instrumental in the establishment of an immune response that promotes tumour progression and holds important implications for integrated therapeutic strategies. However, research into the psychoneuroimmunological benefits of psychosocial intervention is largely missing, and future interdisciplinary research is warranted for understanding and further promoting improved quality of life and psychological as well as physical well-being after psychosocial intervention.Recent studies point to the steadily rising incidence of skin cancers and the pressure rises to identify explanatory models in addition to ultraviolet (UV) radiation exposure and other environmental stressors. Among them, psychosocial stress may play a hitherto underestimated role as several studies suggest that the immune response can be modified by stress and plays a role in the association between coping with a cancer diagnosis, i.e. mental stress, and long-term survival.

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Relations between different coping strategies for social stress, tumor development and neuroendocrine and immune activity in male mice

Cited by 47 publications

References 51 publications

β-adrenoceptors are upregulated in human melanoma and their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell lines

β-adrenoceptors are upregulated in human melanoma and their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell lines

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface

Psychological support of skin cancer patients

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Relations between different coping strategies for social stress, tumor development and neuroendocrine and immune activity in male mice

Cited by 47 publications

References 51 publications

β-adrenoceptors are upregulated in human melanoma and their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell lines

β-adrenoceptors are upregulated in human melanoma and their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell lines

Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal–fetal interface

Psychological support of skin cancer patients

Contact Info

Product

Resources

About

Natural killer cells promote immune tolerance by regulating inflammatory T_H17 cells at the human maternal–fetal interface