Male–female differences in the impact of β-adrenoceptor stimulation on resistance to experimental metastasis: Exploring the effects of age and gonadal hormone involvement

Page, Gayle G.; Fennelly, Andrea M.; Littleton-Kearney, Marguerite T.; Ben‐Eliyahu, Shamgar

doi:10.1016/j.jneuroim.2007.10.023

Cited by 18 publications

(16 citation statements)

References 39 publications

(34 reference statements)

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“…These findings suggest that female F344 rats are more resilient than males to stress-induced NK suppression in general, and specifically to effects mediated through activation of the SNS. These sexual dimorphisms are consistent with our previous studies employing other stress paradigms [48], and specifically with respect to the impact of β-adrenergic receptor activation on NKCC [54, 55]. …”

Section: Discussionsupporting

confidence: 92%

“…These effects are mediated through activation of leukocyte membrane receptors for these ligands, and intracellular initiation of the cAMP-PKA cascade common to both receptor systems [59, 60]. Potentially underlying the aforementioned sex differences in the impact of catecholamines on NKCC are the (i) menstrual cycle and female gonadal hormones that were shown to affect human and rat NK cell susceptibility to adrenergic stimulation [24, 61], presumably through modulating expression levels of adrenergic receptors on leukocytes [62], and (ii) testosterone that was shown to increase rat susceptibility to adrenergic suppression of in vivo levels of NKCC [55]. …”

Section: Discussionmentioning

confidence: 99%

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In vivo suppression of NK cell cytotoxicity by stress and surgery: Glucocorticoids have a minor role compared to catecholamines and prostaglandins

Rosenne

Sorski

Shaashua

et al. 2014

Brain, Behavior, and Immunity

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Most in vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, methodological considerations hinder our ability to deduce from these findings to the impact of endogenous release of these factors on in vivo levels of NKCC and their implications to NK-dependent resistance to pathologies in living humans or animals. Here we used an in vivo approach that sensitively and specifically reflects NKCC in living F344 rats, based on lung clearance of NK-sensitive tumor cells (MADB106), and based on comparing effects between NK-intact and NK-depleted rats. To study the role of corticosterone, epinephrine, and prostaglandins, we administered these factors to rats, or antagonized their endogenous release following different stress paradigms or surgery. The results indicated that endogenous or exogenous elevated corticosterone levels can suppress in vivo NKCC levels, but only under some conditions, and mostly secondarily to the NK-suppressing impact of epinephrine. Specifically, corticosterone-induced NKCC suppression occurred (i) only under prolonged, but not short exposure to stress, and mainly in males; (ii) was smaller than the prominent impact of epinephrine; (iii) was mostly ascribed to corticosterone-induced potentiation of the effects of epinephrine or/and prostaglandins; and (iv) was completely abolished through antagonizing epinephrine or/and prostaglandins. Overall, these findings markedly limit the significance of stress/surgery-induced corticosterone release in the in vivo suppression of NKCC, and highlight the blockade of epinephrine or/and prostaglandins as effective and clinically feasible approaches to overcome such immuno-suppressive effects.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

In vivo suppression of NK cell cytotoxicity by stress and surgery: Glucocorticoids have a minor role compared to catecholamines and prostaglandins

Rosenne

Sorski

Shaashua

et al. 2014

Brain, Behavior, and Immunity

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“…Finally, we and others have reported that male rats are markedly more susceptible to the immunosuppressive and tumor-promoting effects of stress hormones, specifically catecholamines and corticosterone [26,56]. Human studies have reported similar dimorphism with respect to other physiological effects of these hormones.…”

Section: Discussionmentioning

confidence: 55%

“…Such comparisons may yield both practical and theoretical gains with potential clinical ramifications. Because sex differences in the stress responses [25,26], immunity [27] and tumor development [28] are well established, most studies have been conducted in both sexes and included a comparison of the findings in the different sexes.…”

Section: Introductionmentioning

confidence: 99%

The impact of surgical extent and sex on the hepatic metastasis of colon cancer

et al. 2013

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Purpose Extensive oncological surgeries were previously suggested to increase cancer recurrence rates. We herein studied the impact of different surgical procedures and sex on colorectal cancer liver metastasis, employing several tumor-inoculation approaches in BALB/c mice. Methods Experimental hepatic metastases of the syngeneic CT26 colorectal cancer line were induced either by intra-portal inoculation or intrasplenic inoculation, employing different tumor loads. Following intrasplenic inoculation, the entire spleen or an injected hemispleen were removed. Additionally, the magnitude of the surgical trauma accompanying the injection procedure was manipulated. Results Increasing the surgical trauma by adding laparotomy or extending the length of the surgery and hypothermia did not significantly affect the number of liver metastases or liver weight for any of the injection methods and tumor loads. The development of metastasis was significantly greater in males than in females under all conditions studied – a difference not explained by the direct effects of sex hormones on in vitro CT26 proliferation or vitality. Conclusion Concurring with less controlled clinical observations, the surgical extensiveness did not significantly affect CT26 hepatic metastasis, potentially due to a ceiling effect of the surgical trauma on the metastatic process. The sexual dimorphism observed for the CT26 metastasis should be investigated in the context of surgical stress and considering anti-CT26 immunoreactivity.

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“…Enhancement of tumor progression is usually ascribed to b-AR-mediated decrease of NK activity (Shakhar and BenEliyahu 1998;Ben-Eliyahu et al 2000;Ben-Eliyahu et al 2000a), although noradrenaline has also been shown to inhibit the generation of specific antitumor cytotoxic T lymphocytes (Kalinichenko et al 1999). Interestingly, impairment of NK activity and reduced antitumor resistance following stress and b-AR stimulation seem to be affected by age as well as by gender (Page et al 2008). Recently, the prophylactic use of type-C CpG oligodeoxynucleotides (CpG-C ODN) was shown to improve NK activity and immunocompetence, potentially reducing metastatic dissemination after enhanced sympathetic stress responses (Goldfarb et al 2009) and in association with pharmacological blockade of b-ARs and COX inhibition it was proposed as a potential approach to limit postoperative immunosuppression and metastatic progression (Goldfarb et al 2011).…”

Section: Cancermentioning

confidence: 99%