Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors

Juarranz, Marı́a G.; Bolanos, Oscar R.; Gutiérrez‐Cañas, Irene; Lerner, Ethan A.; Robberecht, Patrick; Carmena, Marı́a J.; Prieto, Juan Carlos; Rodríguez-Henche, Nieves

doi:10.1016/s0898-6568(01)00199-1

Cited by 37 publications

(36 citation statements)

References 43 publications

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“…This notion is further supported by the observation that vasoactive intestinal peptide (VIP) can induce the transdifferentiation of LNCaP cells to become NE-like cells by activating protein kinase A, ERK and phosphoinositide 3-kinase (Juarranz et al 2001, Gutierrez-Canas et al 2005. In this study, our data suggest the involvement of RPTPa in this process, providing one of the mechanistic explanations for the clinical observations (Ito et al 2001, Ismail et al 2002, Hirano et al 2004.…”

Section: Discussionsupporting

confidence: 66%

Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells

Yuan¹,

Veeramani²,

Lin³

et al. 2006

Endocr Relat Cancer

148

137

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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 androgenablation 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 androgendeprived conditions. Additionally, we found that receptor protein tyrosine phosphatase a 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.

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Section: Discussionsupporting

confidence: 66%

Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells

Yuan¹,

Veeramani²,

Lin³

et al. 2006

Endocr Relat Cancer

148

137

View full text Add to dashboard Cite

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“…Interestingly, VIP and PACAP analogs have been shown to affect tumor growth in in vitro and in vivo animal tumor models, suggesting that these receptors could be used as novel therapeutic targets or for localization of tumors [116][117][118][119] . The effect of VIP varies with the type of tumor, by either directly promoting tumor growth [76,[120][121][122] , suppressing growth [123] , or promoting its differentiation through VPAC1 receptor signaling [124,125] . More recently, VIP has been shown to modulate tumor cell migration [125] .…”

Section: Resultsmentioning

confidence: 99%

Vasoactive intestinal peptide signaling axis in human leukemia

Dorsam

Benton²,

Failing³

et al. 2011

WJBC

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The vasoactive intestinal peptide (VIP) signaling axis constitutes a master "communication coordinator" between cells of the nervous and immune systems. To date, VIP and its two main receptors expressed in T lymphocytes, vasoactive intestinal peptide receptor (VPAC)1 and VPAC2, mediate critical cellular functions regulating adaptive immunity, including arresting CD4 T cells in G1 of the cell cycle, protection from apoptosis and a potent chemotactic recruiter of T cells to the mucosa associated lymphoid compartment of the gastrointestinal tissues. Since the discovery of VIP in 1970, followed by the cloning of VPAC1 and VPAC2 in the early 1990s, this signaling axis has been associated with common human cancers, including leukemia. This review highlights the present day knowledge of the VIP ligand and its receptor expression profile in T cell leukemia and cell lines. Also, there will be a discussion describing how the anti-leukemic DNA binding transcription factor, Ikaros, regulates VIP receptor expression in primary human CD4 T lymphocytes and T cell lymphoblastic cell lines (e.g. Hut-78). Lastly, future goals will be mentioned that are expected to uncover the role of how the VIP signaling axis contributes to human leukemogenesis, and to establish whether the VIP receptor signature expressed by leukemic blasts can provide therapeutic and/or diagnostic information.

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“…Additionally, treatment of genistein abolishes EGF-induced NE differentiation of DU145 cells (Humez et al 2006), and conditioned media from genistein-induced NE-like LNCaP cells have an inhibitory effect on the growth of PC-3 and DU145 cells (Pinski et al 2006). Vasoactive intestinal peptide (VIP) is a neuropeptide and can also promote NE differentiation of LNCaP cells (Juarranz et al 2001).…”

Section: Other Factors In Ne Differentiationmentioning

confidence: 99%

Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells

Yuan¹,

Veeramani²,

Lin³

2007

Endocr Relat Cancer

213

184

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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.

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Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors

Cited by 37 publications

References 43 publications

Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells

Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells

Vasoactive intestinal peptide signaling axis in human leukemia

Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells

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