Neuroendocrine Differentiation in Prostatic Carcinoma During Hormonal Treatment

Jiborn, Thomas; Bjartell, Anders; Abrahamsson, Per‐Anders

doi:10.1016/s0090-4295(97)00684-5

Cited by 131 publications

(73 citation statements)

References 32 publications

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“…It is well documented that clinical androgen-ablation therapy is associated with increased NE differentiation in prostate carcinomas (Jiborn et al 1998, Ito et al 2001, Ismail et al 2002, Hirano et al 2004. For example, Ito et al (2001) reported that in archival specimens from 137 PCa patients, 70.5% of presence or absence of different concentrations of PP2 as indicated and maintained for an additional 48 h. Total cellular proteins were separated by SDS/PAGE.…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence suggest that NE differentiation is a common feature of prostate carcinogenesis (di Sant'Agnese 1992) and is often associated with tumor progression and poor prognosis (Abrahamsson 1999). For example, as seen in archival clinical specimens, the population of NE cells, both in terms of their numbers and as a percentage, increases, especially in hormonerefractory tumors (Jiborn et al 1998, Ito et al 2001, Ismail et al 2002, Hirano et al 2004. PCa that are composed solely of NE cells, for example small cell carcinomas and carcinoid tumors, are associated with high aggressiveness (Abrahamsson 1999).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

show abstract

“…4 Although the proportion of NE cells present in cancer tissue varies depending on the case, several reports have shown that NE cells and their secretary products (NE factors) are increased in patients with CRPC. 5,6 It is suggested that inappropriate regulation of NE cells might exist in cancer tissue and, particularly, in CRPC. 7 NE tumors of the prostate are heterogeneous, including adenocarcinoma with focal differentiation, carcinoid tumors, and small cell carcinomas (SCCs).…”

mentioning

confidence: 99%

The potential of neurotensin secreted from neuroendocrine tumor cells to promote gelsolin-mediated invasiveness of prostate adenocarcinoma cells

Hashimoto

Kyoda

Tanaka

et al. 2015

Laboratory Investigation

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Neuroendocrine (NE) cells in prostate cancer have been shown to be associated with the progression of prostate cancer. However, little is known about the molecular basis of this association. We have previously demonstrated that NE cells promote metastasis of a human prostate cancer cell line (LNCaP) with overexpression of the gelsolin gene. The purpose of this study was to investigate the interactions between NE cells and LNCaP cells and the involvement of gelsolin in contributing to the invasive potential of LNCaP cells. In addition, we examined whether neurotensin induced gelsolin-mediated invasion. We used the NE cell line NE-CS that was established from the prostate of the LPB-Tag 12T-10 transgenic mouse. Small interfering RNA (siRNA) targeting gelsolin or not targeting it was transfected into LNCaP cells.

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“…[52][53][54][55] For instance, NE differentiation is increased in high-grade and high-stage localized tumors 48,56,57 and is increased even more in androgen-deprived 52 and hormone-refractory cancers. 53 In addition, it has been demonstrated that levels of circulating chromogranin A (CgA), which is a product of prostate NE cells, are higher in patients with prostate cancer than in patients with benign prostatic conditions. In patients with prostate cancer, CgA correlates with both clinical disease stage and the degree to which the cancer has become hormone refractory.…”

Section: Ne Differentiation In Hrpcmentioning

confidence: 99%

“…59 In patients with hormone-refractory disease, elevated serum CgA is a significant predictor of poor prognosis independent of serum PSA and other prognostic factors. 53,54,58,[60][61][62][63] Finally, in a gene-expression profiling experiment of primary prostate cancers, Singh et al demonstrated that the gene for CgA is 1 of 5 genes that correlate strongly with Gleason score and that this 5-gene-expression model alone accurately predicted outcome after radical prostatectomy. 64 The function of NE differentiation has been studied extensively.…”

Section: Ne Differentiation In Hrpcmentioning

confidence: 99%

Is there a role for platinum chemotherapy in the treatment of patients with hormone‐refractory prostate cancer?

Tay

Huang

2006

Cancer

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Docetaxel chemotherapy is the current standard of care for metastatic hormone-refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin and carboplatin, have moderate single-agent activity in HRPC. Next-generation platinum drugs, including satraplatin and oxaliplatin, may have additional activity in the management of HRPC. Furthermore, neuroendocrine differentiation may play a role in disease progression, providing a rationale for platinum-based chemotherapy in the management of HRPC. The authors reviewed the MEDLINE database for reports related to platinum-based chemotherapy in patients with advanced prostate cancer and evaluated studies that reviewed the role of neuroendocrine differentiation in the progression of HRPC. Older studies from the 1970s and 1980s suggested a lack of activity of cisplatin and carboplatin; however, those studies were flawed at least in part by their methods of response assessment. More recent Phase II studies of carboplatin suggested a moderate level of clinical and palliative activity when it was used as a single agent. However, when carboplatin was combined with a taxane and estramustine, high response rates were observed in several recent clinical trials. In addition, a randomized trial suggested that satraplatin plus prednisone improved progression-free survival compared with prednisone alone. For patients who progressed after docetaxel, no standard options existed in the literature that was reviewed. Several preliminary reports suggested that carboplatin and oxaliplatin may have activity as second-line chemotherapy. Platinum chemotherapy drugs historically have been considered inactive in HRPC, although a review of the data suggested otherwise. Carboplatin, in particular, induced very high response rates when it was combined with estramustine and a taxane, but it also appeared to have activity in patients who progressed after docetaxel. Satraplatin plus prednisone is being investigated in a large Phase III trial as second-line chemotherapy for HRPC. Targeting neuroendocrine cells may provide a new therapeutic approach to HRPC.

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Neuroendocrine Differentiation in Prostatic Carcinoma During Hormonal Treatment

Cited by 131 publications

References 32 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

The potential of neurotensin secreted from neuroendocrine tumor cells to promote gelsolin-mediated invasiveness of prostate adenocarcinoma cells

Is there a role for platinum chemotherapy in the treatment of patients with hormone‐refractory prostate cancer?

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