Neuronal Trans-Differentiation in Prostate Cancer Cells

Area of Science:

• Oncology
• Neuroscience
• Molecular Biology

Background:

• Neuroendocrine (NE) differentiation in prostate cancer (PCa) signifies an aggressive phenotype.
• This phenotype is associated with resistance to therapy.
• The complete cellular phenotype of NE prostate cancer is not well understood.

Purpose of the Study:

• To analyze the phenotype of NE carcinoma of the prostate.
• To understand the cellular mechanisms underlying NE differentiation in prostate cancer.

Main Methods:

• In vitro studies using LNCaP cells subjected to stressors (low serum, cAMP).
• In silico analysis of human prostate cancer data.
• Immunohistochemical analysis of human prostate cancer tissues.
• Gene array and gene ontology analysis.

Main Results:

• LNCaP cells exhibited neuronal trans-differentiation with neuronal morphology and marker expression under stress.
• Gene expression analysis revealed a human brain gene signature in stressed LNCaP cells.
• In silico analysis confirmed enrichment of this 'brain profile' in hormone-resistant metastatic prostate cancer.
• Neuronal differentiation pathways were identified through gene ontology analysis.

Conclusions:

• Prostate cancer evolution may involve neuronal trans-differentiation in later stages.
• This trans-differentiation could allow cancer cells to gain independence from the neural axis.
• Neuronal markers were validated in human prostate cancer tissues.