Faculty Collaboration Database

Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells. Endocr Relat Cancer 2006 Mar;13(1):151-67

Date

04/08/2006

Pubmed ID

16601285

DOI

10.1677/erc.1.01043

Scopus ID

2-s2.0-33645971015 (requires institutional sign-in at Scopus site)   126 Citations

Abstract

Neuroendocrine (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.

Author List

Yuan TC, Veeramani S, Lin FF, Kondrikou D, Zelivianski S, Igawa T, Karan D, Batra SK, Lin MF

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Androgens
Animals
Cell Differentiation
Chromogranin A
Chromogranins
Epithelial Cells
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neurotensin
Parathyroid Hormone-Related Protein
Phosphopyruvate Hydratase
Prostate-Specific Antigen
Prostatic Neoplasms
Protein Tyrosine Phosphatases
Receptor-Like Protein Tyrosine Phosphatases, Class 4
Receptors, Androgen
Receptors, Cell Surface
Tumor Cells, Cultured