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Prostate cancer progression attributed to autonomic nerve development: potential for therapeutic prevention of
Elena V Fernández1, Douglas K Price, William D Figg
1Molecular Pharmacology Section; Medical Oncology Branch; National Cancer Institute; Bethesda, MD USA.
Abstract:
In a study recently published in Science, Magnon et al. show that both the sympathetic and parasympathetic components of the autonomic nervous system play an integral part in the development and dissemination of prostate cancer (PCa). Inhibition of the sympathetic nervous system (SNS) and disruption of the adrenergic receptors, specifically Ardβ 2, resulted in the prevention of primary PCa tumor development in mice. The authors found that inhibition of the SNS is only successful in preventing murine tumor development if completed early enough, and the parasympathetic nervous system (PNS) predominates in later stages of PCa. Inhibition of the PNS by way of the cholinergic receptor, muscarinic 1 (Chrm1), caused mice to develop less metastases to the pelvic lymph nodes, intestines, and bones. A PCa progression scheme has been outlined where initial tumor engraftment is controlled by the SNS but then becomes less prominent than the PNS, which promotes metastasis. The investigators showed the dependence of the autonomic nervous system on development of PCa and present opportunities for prevention; further studies are needed to confirm these results in humans.
Insights
The sympathetic and parasympathetic nervous systems influence prostate cancer (PCa) progression. Targeting these systems, particularly early sympathetic nervous system inhibition, may prevent tumor development and metastasis.
Area of Science:
- Oncology
- Neuroscience
- Urology
Background:
- Prostate cancer (PCa) is a leading cause of cancer death in men.
- The role of the autonomic nervous system (ANS) in PCa development and metastasis is not fully understood.
- The ANS comprises the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS).
Purpose of the Study:
- To investigate the integral role of both the sympathetic and parasympathetic nervous systems in prostate cancer development and dissemination.
- To explore potential therapeutic strategies targeting the ANS for PCa prevention and treatment.
Main Methods:
- Utilized a mouse model to study PCa development and metastasis.
- Inhibited the sympathetic nervous system (SNS) by targeting adrenergic receptors (specifically Ardβ2).
- Inhibited the parasympathetic nervous system (PNS) by targeting cholinergic receptors (specifically muscarinic 1, Chrm1).
Main Results:
- Early inhibition of the SNS prevented primary PCa tumor development in mice.
- The SNS was found to control initial tumor engraftment.
- The PNS predominates in later stages, promoting metastasis to pelvic lymph nodes, intestines, and bones.
- Inhibition of the PNS reduced metastatic spread.
Conclusions:
- The autonomic nervous system plays a critical, stage-dependent role in prostate cancer progression.
- Targeting the SNS and PNS presents potential avenues for PCa prevention and treatment.
- Further research is required to validate these findings in human patients.
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