Treatment With β-Blockers and Reduced Disease Progression in Patients With Thick Melanoma

Giorgi, Vincenzo De; Grazzini, Marta; Gandini, Sara; Benemei, Silvia; Lotti, Torello; Marchionni, Niccolò; Geppetti, Pierangelo

doi:10.1001/archinternmed.2011.131

Cited by 151 publications

(134 citation statements)

References 10 publications

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“…15,16 The use of b-blockers, on the other hand, has been associated with prolonged survival in women treated for breast cancer, [17][18][19][20] as well as in patients affected with prostate, 21,22 lung, 23 ovarian 24 and cutaneous melanoma. 25,26 A commonality among these studies is that the conditions and drugs involved affect the sympathetic nervous system (SNS), whose activity is stimulated by chronic stress and depression and inhibited by b-blockers.…”

Section: Neuroendocrine Factors and Bone Metastasismentioning

confidence: 99%

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Elefteriou¹

2015

BoneKEy Reports

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Improved detection programs and new therapies significantly improved the 5-year survival rate of women with breast cancer. However, some women still relapse and succumb to cancer because of metastatic disease. In particular, chronically depressed patients do not seem to benefit from newly developed treatments and present with shorter survival. The reason for this association is unclear, but recent cues from preclinical studies point to the possible contribution of neuroendocrine factors generated in response to chronic stress and depression. Retrospective clinical studies also suggest a beneficial effect of sympathetic blockade in terms of less advanced disease at diagnosis, lower cancer-specific mortality, longer disease-free survival and reduced metastasis development and tumor recurrence, especially in patients who have taken propranolol before diagnosis. Therefore, b-blockers or therapies normalizing sympathetic tone might be beneficial as early adjuvant therapies to limit skeletal metastases and growth and eventually to improve prognosis in patients with breast cancers.

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Section: Neuroendocrine Factors and Bone Metastasismentioning

confidence: 99%

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Elefteriou¹

2015

BoneKEy Reports

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“…11 In addition, recent evidence suggests a dramatic role of b-AR blockers in reducing metastases, tumour recurrence and specific mortality in breast cancer patients. 12 More recently, the use of b-blockers for concomitant disease was associated with a reduced risk of progression of thick melanoma 13 and with an increased survival time of melanoma patients, 14 suggesting that the interaction of catecholamines with b-ARs could be a useful target in this disease.…”

mentioning

confidence: 99%

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

107

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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“…Indeed, data from many epidemiologic and experimental studies have revealed that the β-adrenergic receptor signaling pathway was involved in the proliferation, metastasis, and angiogenesis of several types of tumors [34][35][36]. Accumulating evidence has indicated that IH is a powerful sympathetic activator [37,38].…”

Section: Discussionmentioning

confidence: 99%

Accelerated tumor growth under intermittent hypoxia is associated with hypoxia-inducible factor-1-dependent adaptive responses to hypoxia

Yoon

Min

et al. 2017

Sleep Medicine

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Treatment With β-Blockers and Reduced Disease Progression in Patients With Thick Melanoma

Cited by 151 publications

References 10 publications

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

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

Accelerated tumor growth under intermittent hypoxia is associated with hypoxia-inducible factor-1-dependent adaptive responses to hypoxia

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