Influence of the neural microenvironment on prostate cancer

Christian Coarfa, Diego Florentin, Nagi Reddy Putluri, Yi Ding, Jason Au, Dandan He, Ahmed Ragheb, Anna Frolov, George Michailidis, Min Jae Lee, Dov Kadmon, Brian J. Miles, Christopher Smith, Michael Ittmann, David Rowley, Arun Sreekumar, Chad J. Creighton, Gustavo Ayala

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Background: Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. Method: We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. Result: Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non-neoplastic epithelial cells. Conclusion: Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer.

Original languageEnglish (US)
Pages (from-to)128-139
Number of pages12
Issue number2
StatePublished - Feb 1 2018


  • Botox
  • cancer
  • denervation
  • nerves
  • neurogenesis
  • prostate
  • Neoplasm Invasiveness
  • Male
  • Tumor Burden
  • Disease Progression
  • Animals
  • Energy Metabolism
  • Tumor Microenvironment/physiology
  • Botulinum Toxins, Type A/pharmacology
  • Prostatic Neoplasms/pathology
  • Mice
  • Denervation/methods
  • Prostate/innervation
  • Acetylcholine Release Inhibitors/pharmacology
  • Disease Models, Animal

ASJC Scopus subject areas

  • Urology
  • Oncology


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