Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade

Partecke, Lars Ivo; Speerforck, Sven; Käding, André; Seubert, Florian; Kühn, Sandra; Lorenz, Eric; Schwandke, Sebastian; Sendler, Matthias; Keßler, Wolfram; Trung, Dung Nguyen; Oswald, Stefan; Weiß, Frank Ulrich; Mayerle, Julia; Henkel, Christin; Menges, Pia; Beyer, Katharina; Lerch, Markus M.; Heidecke, Claus–Dieter; Bernstorff, Wolfram von

doi:10.1016/j.pan.2016.03.005

Cited by 98 publications

(89 citation statements)

References 63 publications

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“…Mounting clinical and preclinical evidence has shown that psychosocial factors can trigger chronic adrenergic signaling within tumors and promote tumor growth and metastasis in many tumor types (1)(2)(3)(4)(5). Activation of the sympathetic nervous system leads to release of stress hormones such as epinephrine and norepinephrine (NE), which signal via adrenergic receptors on tumor cells, resulting in diminished efficacy of conventional chemotherapy and promotion of tumor metastasis, inflammation, and other prosurvival pathways (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens

Nagaraja¹,

Dood²,

Armaiz-Peña³

et al. 2017

JCI Insight

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Section: Introductionmentioning

confidence: 99%

Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens

Nagaraja¹,

Dood²,

Armaiz-Peña³

et al. 2017

JCI Insight

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“…Partecke et al also investigated the impact of chronic stress on pancreatic cancer growth using C57BL/6 mice bearing orthotopic syngeneic 6606PDA tumours [54]. Stress was shown to be associated with immunosuppression and an increase in tumour angiogenesis and cancer cell invasion.…”

Section: Pre-clinical Evidence In Cancer - In Vitro and In Vivomentioning

confidence: 99%

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

Pantziarka

Bouche

Sukhatme³

et al. 2016

ecancer

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Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers.

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“…With cancer being the second leading cause of death in the U.S. and globally, having shifting underlying contributors to this burden 28-30 , a prospective analysis examining the association of an index of MSBR with cancer mortality would address a major gap in the literature. It would also allow for the ability to triangulate population-level evidence with in vivo and in vitro studies of stress and cancer outcomes 14,31,32 . Furthermore, it may also have clinical utility for cancer prediction, as the index relies upon commonly measured biomarkers to address this gap.…”

mentioning

confidence: 99%

Multi-Systemic Biological Risk and Cancer Mortality: The NHANES III Study

Acheampong

Jiang

Ziogas

et al. 2020

Sci Rep

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Multi-systemic biological risk (MSBR), a proxy for allostatic load, is a composite index of biomarkers representing dysregulation due to responses to chronic stress. this study examined the association of an MSBR index with cancer mortality. the sample included n = 13,628 adults aged 20-90 from the NHANES III Linked Mortality File (1988)(1989)(1990)(1991)(1992)(1993)(1994). The MSBR index included autonomic (pulse rate, blood pressure), metabolic (HoMA ir , triglycerides, waist circumference), and immune (white blood cell count, C-reactive protein) markers. We fit Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of overall cancer mortality risk, according to quartiles (q) of the index. In multivariable models, compared to those in q1, q4 had a 64% increased risk for cancer mortality (HR = 1.64, 95% CI:1.13-2.40). The immune domain drove the association (HR per unit = 1.19, 95% CI:1.07-1.32). In stratified analyses, the HR for those with a BMI ≥ 25 was 1.12 per unit (95% CI:1.05-1.19) and those with a BMI < 25 was 1.04 per unit (95% CI:0.92-1.18). MSBR is positively associated with risk for cancer mortality in a US sample, particularly among those who are overweight or obese. The utilization of standard clinical measures comprising this index may inform population cancer prevention strategies.Multi-systemic biological risk (MSBR) is a proxy for allostatic load (AL). It is a metric of health risk that captures the complex biological cascade that occurs in autonomic, metabolic, and immune domains in response to chronic environmental and psychosocial stress 1-3 . The validity of the AL construct is established and demonstrates common variance and statistical coherence between, prominent primary mediators of the stress response (i.e., stress hormones), and secondary mediators reflecting the resulting biological alterations in autonomic, metabolic, and immune domains that accumulate over time [4][5][6][7][8] . Importantly, summary AL indices have demonstrated a non-additive, stronger magnitude of association with outcomes compared with the individual components of the index 9 .Previous research has shown that autonomic, metabolic, and immune disorders, share common risk factors with cancer outcomes 10-12 . Moreover, there is a strong physiological link between over-activation of the stress response and regulation of the tumor microenvironment [13][14][15] . In mechanistic animal studies where stress can demonstrably be reproduced, chronic responses to stress influence processes involved in tumorigenesis [16][17][18][19] . However, observational studies assessing self-report of stressful life events and cancer outcomes have generally been inconsistent [20][21][22][23][24][25] .Epidemiological studies show positive associations between higher levels of AL indices and cardiovascular disease (CVD), as well as mortality risk 26,27 . However, we are not aware of any studies that have examined an index of AL with cancer outcomes. With cancer being the second leading cause of de...

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Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade

Cited by 98 publications

References 63 publications

Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens

Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

Multi-Systemic Biological Risk and Cancer Mortality: The NHANES III Study

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