Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas

Abstract

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.

Effect of the autonomic nervous system on cancer progression depends on the type of tumor: solid are more affected then ascitic tumors

“…Using several experimental approaches (surgical as well as pharmacological), we have investigated the participation of sympathetic and parasympathetic nerves in cancer development and progression. Th e results obtained from our experimental studies have supported the stimulatory role of the sympathetic neurotransmission in the case of an intra-abdominal rat fi brosarcoma (Lackovicova et al 2011) and subcutaneous murine melanoma (Horvathova et al 2016b). However, the involvement of the parasympathetic nerves in growth of rat intra-abdominal fi brosarcoma has not been observed .…”

“…In mice sacrifi ced in earlier stage of melanoma growth (on the 20 th day aft er B16-F10 melanoma cells injection), 6-OHDA treatment resulted in a signifi cant reduction of the tumor mass when compared to animals with the intact sympathetic nerves (Horvathova et al 2016a). Interestingly, in survival st udy we found that weight of the developed melanoma tissue in sympathectomized animals was signifi cantly increased in comparison with vehicle group animals (Horvathova et al 2016b).…”

“…Median survival of melanoma-bearing mice was without 6-OHDA treatment 29 days and aft er 6-OHDA treatment 34 days. However, there was no diff erence in the incidence of melanoma in mice with intact sympathetic nerves (100% incidence of tumors -all animals injected with melanoma cells had developed tumor) and sympathectomized mice (two animals from all injected with melanoma cells did not develop tumor that represents 92.6% (Horvathova et al 2016b). Moreover, the eff ect of the chemical sympathectomy on the melanoma progression was assessed also by weighting of developed melanoma mass.…”

Association of tyrosine hydroxylase expression in brain and tumor with increased tumor growth in sympathectomized mice

“…Regarding tumor progression, Horvathova et al [10,13] reported contradicting results on the effect of sympathectomy on tumor growth in a melanoma model. They found that sympathectomy delayed tumor development and significantly prolonged the survival of tumor-bearing mice.…”

“…Body mass index (BMI) was calculated at the end of the protocol as the product of dividing the corrected body weight between the square of the nose-anus length [9]. The general state of health of experimental animals was daily monitored, including known 6-OHDA side-effects such as ptosis (upper eyelid drooping) and presence of blood in urine [10].…”