Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Batra, Surinder K.
MetadataShow full item record
AbstractNeuroendocrine (NE) cells are the minor cell populations in normal prostate epithelial compartments. During prostate carcinogenesis, the number of NE cells in malignant lesions increases, correlating with its tumorigenicity and hormone-refractory growth. It is thus proposed that cancerous NE cells promote prostate cancer (PCa) cell progression and its androgen-independent proliferation, although the origin of the cancerous NE cells is not clear. To investigate the role of cancerous NE cells in prostate carcinogenesis, we characterized three NE subclone cell lines-NE-1.3, NE-1.8 and NE-1.9, which were transdifferentiated from androgen-sensitive human PCa LNCaP cells by culturing in an androgen-depleted environment, resembling clinical androgen-ablation therapy. These subclone cells acquire many features of NE cells seen in clinical prostate carcinomas, for example exhibiting a neuronal morphology and expressing multiple NE markers, including neuron-specific enolase, chromogranin B, neurotensin, parathyroid hormone-related peptide, and to a lesser degree for chromogranin A, while lacking androgen receptor (AR) or prostate specific antigen (PSA) expression. These cells represent terminally differentiated stable cells because after 3 months of re-culturing in a medium containing androgenic activity, they still retained the NE phenotype and expressed NE markers. Despite these NE cells having a slow growth rate, they readily developed xenograft tumors. Furthermore, media conditioned by these NE cells exhibited a stimulatory effect on proliferation and PSA secretion by LNCaP cells in androgen-deprived conditions. Additionally, we found that receptor protein tyrosine phosphatase alpha plays a role in upregulating multiple NE markers and acquiring the NE phenotype. These NE cells thus represent cancerous NE cells and could serve as a useful cell model system for investigating the role of cancerous NE cells in hormone-refractory proliferation of PCa cells.
CitationEndocr. Relat. Cancer 2006, 13 (1):151-167
DescriptionKEYWORDS CLASSIFICATION: Adenocarcinoma;Androgens;Animals;Biology;Cell Differentiation;Chromogranin A;Chromogranins;Epithelial Cells;Humans;metabolism;Male;mechanisms of carcinogenesis;Mice;Mice,Inbred BALB C;Mice,Nude;Molecular Biology;Neurotensin;pathology;physiology;Parathyroid Hormone-Related Protein;Phosphopyruvate Hydratase;Prostate-Specific Antigen;Prostatic Neoplasms;Protein-Tyrosine-Phosphatase;Receptors,Androgen;Receptors,Cell Surface;Research;secretion;therapy;Tumor Cells,Cultured.
- Acquisition of neuroendocrine characteristics by prostate tumor cells is reversible: implications for prostate cancer progression.
- Authors: Cox ME, Deeble PD, Lakhani S, Parsons SJ
- Issue date: 1999 Aug 1
- Neuroendocrine differentiation in prostate carcinoma: focusing on its pathophysiologic mechanisms and pathological features.
- Authors: Alberti C
- Issue date: 2010 Nov-Dec
- Androgen deprivation of the PC-310 [correction of prohormone convertase-310] human prostate cancer model system induces neuroendocrine differentiation.
- Authors: Jongsma J, Oomen MH, Noordzij MA, Van Weerden WM, Martens GJ, van der Kwast TH, Schröder FH, van Steenbrugge GJ
- Issue date: 2000 Feb 1
- NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice.
- Authors: Jin RJ, Wang Y, Masumori N, Ishii K, Tsukamoto T, Shappell SB, Hayward SW, Kasper S, Matusik RJ
- Issue date: 2004 Aug 1
- Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells.
- Authors: Yuan TC, Veeramani S, Lin MF
- Issue date: 2007 Sep