Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells.
Neuroendocrine (NE) cells represent a minor cell population in the epithelial compartment of normal prostate glands and may play a role in regulating the growth and differentiation of normal prostate epithelia. In prostate tumor lesions, the population of NE-like cells, i.e., cells exhibiting NE phenotypes and expressing NE markers, is increased that correlates with tumor progression, poor prognosis, and the androgen-independent state. However, the origin of those NE-like cells in prostate cancer (PCa) lesions and the underlying molecular mechanism of enrichment remain an enigma. In this review, we focus on discussing the distinction between NE-like PCa and normal NE cells, the potential origin of NE-like PCa cells, and in vitro and in vivo studies related to the molecular mechanism of NE transdifferentiation of PCa cells. The data together suggest that PCa cells undergo a transdifferentiation process to become NE-like cells, which acquire the NE phenotype and express NE markers. Thus, we propose that those NE-like cells in PCa lesions were originated from cancerous epithelial cells, but not from normal NE cells, and should be defined as 'NE-like PCa cells'. We further describe the biochemical properties of newly established, stable NE-like lymph node carcinoma of the prostate (LNCaP) cell lines, transdifferentiated from androgen-sensitive LNCaP cells under androgen-deprived conditions. Knowledge of understanding NE-like PCa cells will help us to explore new therapeutic strategies for treating PCa.
Yuan
Ta-Chun
TC
Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, Nebraska 68198-5870, USA.
Veeramani
Suresh
S
Lin
Ming-Fong
MF
D000230:Adenocarcinoma / Q000473:pathology*; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D000242:Cyclic AMP / Q000819:agonists / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D018358:Neuroendocrine Tumors / Q000473:pathology*; D009490:Neurosecretory Systems / Q000166:cytology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D000728:Androgens; D016207:Cytokines; D015850:Interleukin-6; D000242:Cyclic AMP; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4