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Updated: Aug 20, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas
Objectives:
Previously we have shown that 20 days after 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 find out how long the suppressing effect of sympathectomy on the melanoma growth may endure.
Methods:
The 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. Then, melanoma development, survival of the tumor-bearing 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 significantly prolonged the survival of the tumor-bearing mice (median 34 days vs. 29 days). However, the weight of the developed melanoma was significantly increased in the sympathectomized mice in comparison with the animals having intact sympathetic nervous system.
Conclusions:
The data of the present study showed that effect 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, specifically 20 days after melanoma cells injection, now we indicate that in later stages of the melanoma progression, the tumor mass was significantly increased in sympathectomized animals. These contra-intuitive findings may indicate that interventions affecting the sympathetic nervous system may exert complex effect on the tumor progression. Based on these data we may suggest that the potential therapeutic interventions affecting 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.
Insights
Chemical sympathectomy in mice delayed melanoma development and prolonged survival, but increased tumor mass later on. This suggests complex effects of sympathetic nervous system modulation on cancer progression.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- Previous studies indicated smaller melanomas in chemically sympathectomized mice.
- Chemical sympathectomy's effect on sympathetic neurotransmission is temporary.
- The duration of sympathectomy's suppressive effect on melanoma growth requires further investigation.
Purpose of the Study:
- To determine the long-term impact of chemical sympathectomy on melanoma progression and survival in mice.
- To assess how long the melanoma-suppressing effect of sympathectomy endures.
- To investigate the complex relationship between sympathetic nervous system activity and melanoma growth.
Main Methods:
- Male C57BL/6J mice underwent chemical sympathectomy using 6-hydroxydopamine.
- B16-F10 melanoma cells were injected subcutaneously seven days post-sympathectomy.
- Melanoma development, tumor weight, and mouse survival were analyzed.
Main Results:
- Sympathectomy delayed tumor onset (day 18 vs. 14) and significantly extended median survival (34 days vs. 29 days).
- Despite prolonged survival, the weight of developed melanoma was significantly increased in sympathectomized mice.
- These findings contrast with earlier observations of reduced tumor mass at 20 days post-injection.
Conclusions:
- Chemical sympathectomy's effects persisted beyond nerve regeneration, prolonging mouse survival.
- Later-stage melanoma progression showed increased tumor mass in sympathectomized mice, indicating complex effects.
- Therapeutic strategies targeting sympathetic signaling should aim for sustained attenuation to potentially achieve complete tumor regression.
