Sympathectomy suppresses tumor growth and alters gene‐expression profiles in rat tongue cancer

Raju, Bina; Hultström, Michael; Haug, Sivakami Rethnam; Ibrahim, Mohamed Yousif; Heyeraas, Karin J.

doi:10.1111/j.1600-0722.2009.00646.x

Cited by 22 publications

(29 citation statements)

References 34 publications

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“…Stimulatory eff ect of the sympathetic nervous system on the tumor growth and development of metastasis has been further supported by experimental and clinical studies, in which sympathetic neurotransmission was attenuated or eliminated (Raju et al 2009;Sloan et al 2010;Barron et al 2011;Lackovicova et al 2011;Magnon et al 2013). Based on these facts, it has been suggested that interventions reducing the eff ect of the sympathetic neurotransmitters may represent a potential adjuvant therapy in oncological patients (Schuller 2010;Powe and Entschladen 2011;Tang et al 2013).…”

mentioning

confidence: 80%

“…For example, chemical sympathectomy performed by 6-OHDA attenuated the incidence of N-methyl-N´-nitro-N-nitrosoquanidine (MNNG) induced gastric cancer in rats (Tatsuta et al 1992), inhibited the growth pattern of LPC-1 plasmacytoma tumors in mice (Grzanna et al 1985), and also decreased the incidence of intra-abdominal fi brosarcoma tumors in rats and prolonged their survival (Lackovicova et al 2011). Similarly, bilateral surgical sympathectomy in rats resulted in the development of significantly smaller and less invasive tongue tumors than in sham-operated animals (Raju et al 2007;Raju et al 2009). Moreover, pre-treatment of tumor-bearing rats with β-blockers signifi cantly reduced the development of tumors in stressed animals as well as development of metastases aft er surgical removal of the tumor mass (Sloan et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Th ey have found 280 genes diff erentially expressed in tumors with intact sympathetic innervation compared with the bilaterally sympathectomized tumors. Alterations have been found in genes associated with the cell adhesion and signalling structure, proliferation, metabolism, lymphangiogenesis, growth and development, and immunity (Raju et al 2009). Similarly, we also found in melanoma tissue changes in expression profi le of many genes related to cancer-limiting processes, such as apoptosis, hypoxia, and angiogenesis, induced by chemical denervation in mice (Horvathova et al 2016).…”

Section: Discussionmentioning

confidence: 99%

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Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas

Horváthová

Tillinger

Padová

et al. 2016

Endocrine Regulations

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Objectives.Previously we have shown that 20 days aft er the tumor cells injection smaller melanomas have been developed in chemically sympathectomized mice in comparison with animals having intact sympathetic nervous system. However, it is known that chemical sympathectomy reduces the sympathetic neurotransmission only temporarily. In the present study, we monitored the survival of the sympathectomized mice with melanoma with an attempt to fi nd out how long the suppressing eff ect of sympathectomy on the melanoma growth may endure.Methods. Th e chemical sympathectomy was performed by intraperitoneal injection of neurotoxin 6-hydroxydopamine in male C57BL/6J mice. Seven days later, the animals were injected subcutaneously with B16-F10 melanoma cells. Th en, melanoma development, survival of the tumorbearing mice and weight of the developed tumor mass were analyzed.Results. Sympathectomy delayed the development of the palpable tumors (18th day vs.14th day) and signifi cantly prolonged the survival of the tumor-bearing mice (median 34 days vs. 29 days). However, the weight of the developed melanoma was signifi cantly increased in the sympathectomized mice in comparison with the animals having intact sympathetic nervous system.Conclusions. Th e data of the present study showed that eff ect of the chemical sympathectomy, performed before the tumor growth induction, persisted even at the time when sympathetic nerves started to regenerate that resulted in a prolonged survival of the mice with melanoma. However, comparing to our previous study, in which we have shown a reduced tumor mass in earlier stages of the tumor growth, specifi cally 20 days aft er melanoma cells injection, now we indicate that in later stages of the melanoma progression, the tumor mass was signifi cantly increased in sympathectomized animals. Th ese contra-intuitive fi ndings may indicate that interventions aff ecting the sympathetic nervous system may exert complex eff ect on the tumor progression. Based on these data we may suggest that the potential therapeutic interventions aff ecting the sympathetic signaling in the tumor tissue and its microenvironment should attenuate the sympathetic neurotransmission not only temporarily but till the complete regression of the tumor tissue.

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confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas

Horváthová

Tillinger

Padová

et al. 2016

Endocrine Regulations

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“…The inhibitory effect of reduced sympathetic activity on tumor growth has been widely documented. It was found out that bilaterally sympathectomized rats developed significantly smaller and less invasive tongue tumors than the animals of sham-operated group (Raju et al, 2007(Raju et al, , 2009. Likewise, in a model where mammary tumors were induced subcutaneously in a sympathetically denervated ear, the tumor growth was attenuated approximately by over 50% compared with the contralateral induction in intact ear.…”

Section: Discussionmentioning

confidence: 90%

Chemical sympathectomy increases neutrophil-to-lymphocyte ratio in tumor-bearing rats but does not influence cancer progression

Horváthová

Tillinger

Sivakova

et al. 2015

Journal of Neuroimmunology

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“…For example, the growth of oral cancers was significantly inhibited by sympathectomy [14]. This impairment of tumor growth induced by denervation was associated with changes in multiple processes, including alteration of the VEGF pathway [15]. Importantly, the sympathetic activity is known to be stimulated by hypoxic conditions [16].…”

Section: Introductionmentioning

confidence: 98%

Sympathetic Signaling in Angiogenesis: Implications for Cancer Progression

Tilan¹,

Czarnecka²,

Kitlińska³

2012

CCTR

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Sympathetic neurotransmitters are known for their multiple and pleiotropic functions. Recently, regulation of tumor angiogenesis emerged as one of them. Norepinepherine and epinephrine have been shown to stimulate tumor vascularization via two independent mechanisms -induction of growth factor release from tumor and stromal cells, and a direct effect on endothelial cell (EC) proliferation. In contrast, their precursor, dopamine, interferes with vascular endothelial growth factor (VEGF) signaling in ECs and inhibits angiogenesis. Tumor vascularization can be also regulated by peptidergic neurotransmitters, such as neuropeptide Y (NPY), which acts as a potent angiogenic factor due to its direct stimulatory effect on EC proliferation, migration and capillary formation. The angiogenic activity of these neuronal factors is particularly apparent under the conditions of increased sympathetic activity during stress, or in tumors of sympathetic origin. However, there is also evidence indicating that basal sympathetic activity is essential for sustained growth of nonneuronal tumors. Importantly, sympathetic activity increases in hypoxia, which is a crucial factor inducing neovascularization. Moreover, in tumor cells, adrenergic stimulation up-regulates hypoxia-inducible factor 1 (HIF-1 ) independently on oxygen levels, which mimics hypoxic conditions and increases the release of angiogenic factors. The pro-and antiangiogenic effects of sympathetic neurotransmitters are potent enough to alter rates of tumor growth and metastases, confirming their potential value as therapeutic targets. However, such therapy may be complicated by other activities of these neuronal factors, such as immunomodulation and direct effects on tumor cell functions, which are tumor specific and may both facilitate and inhibit tumor growth.

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Sympathectomy suppresses tumor growth and alters gene‐expression profiles in rat tongue cancer

Cited by 22 publications

References 34 publications

Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas

Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas

Chemical sympathectomy increases neutrophil-to-lymphocyte ratio in tumor-bearing rats but does not influence cancer progression

Sympathetic Signaling in Angiogenesis: Implications for Cancer Progression

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