Prognostic Significance of Neuroendocrine Differentiation in Prostate Adenocarcinoma

Sağnak, Levent; Topaloğlu, Hikmet; Özok, Uğur; Ersoy, Hamit

doi:10.1016/j.clgc.2011.07.003

Cited by 39 publications

(42 citation statements)

References 94 publications

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“…Castrate resistance mechanisms are complex and influenced by multiple endogenous and exogenous signals encompassing NED. Indeed, a high percentage of NE-differentiated cells are present in prostatic tissue and high concentrations of NE markers are measurable in the blood in castrate-resistant states (Sagnak et al 2011). NE-differentiated cells secrete somatostatin, 5-hydroxytryptamine (serotonin), bombesin, calcitonin and parathyroid hormone-related protein, which have all been associated with PCa progression (Sagnak et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…MIF sustains AKTand ERK1/2 signalling pathways, and the expression of markers involved in proliferation, survival and metastasis NE cell differentiation is probably linked to PCa progression (Jin et al 2004, Sagnak et al 2011. Moreover, MIF has been shown to activate the AKT and ERK1/2 pathways in several cell types (Mitchell et al 1999, Lue et al 2007).…”

Section: Adenoviral-derived Mif Overexpression Sustains Proliferationmentioning

confidence: 99%

“…All adenocarcinomas of the prostate contain some NE cells, and about 10% have abundant NE cells (Abrahamsson et al 1987). NE differentiation (NED) is increased in high-grade and high-stage tumours, and particularly in hormonally treated tumours and castrate-resistant tumours (Sun et al 2009, Sagnak et al 2011. NE tumour cells do not express the androgen receptor (AR) that may favour tumour cell survival during androgen deprivation.…”

Section: Introductionmentioning

confidence: 99%

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Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells

Tawadros

Alonso

Jichlinski

et al. 2012

Endocrine-Related Cancer

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The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PCa) cells is closely related to tumour progression and hormone resistance. The mechanisms by which NE cells influence PCa growth and progression are not fully understood. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in oncogenic processes, and MIF serum levels correlate with aggressiveness of PCa. Here, we investigated the regulation and the functional consequences of MIF expression during NE transdifferentiation of PCa cells. NE differentiation (NED) of LNCaP cells, initiated either by increasing intracellular levels of cAMP or by culturing cells in an androgen-depleted medium, was associated with markedly increased MIF release. Yet, intracellular MIF protein and mRNA levels and MIF gene promoter activity decreased during NED of LNCaP cells, suggesting that NED favours MIF release despite decreasing MIF synthesis. Adenoviral-mediated forced MIF expression in NE-differentiated LNCaP cells increased cell proliferation without affecting the expression of NE markers. Addition of exogenous recombinant MIF to LNCaP and PC-3 cells stimulated the AKT and ERK1/2 signalling pathways, the expression of genes involved in PCa, as well as proliferation and resistance to paclitaxel and thapsigargin-induced apoptosis. Altogether, these data provide evidence that increased MIF release during NED in PCa may facilitate cancer progression or recurrence, especially following androgen deprivation. Thus, MIF could represent an attractive target for PCa therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Adenoviral-derived Mif Overexpression Sustains Proliferationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells

Tawadros

Alonso

Jichlinski

et al. 2012

Endocrine-Related Cancer

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show abstract

“…This is the case for prostate cancer, which is frequently characterized by NE differentiation [107,108]. In prostate cancer, NE differentiation is usually correlated with a poor prognosis [109], probably due to the fact that NE cells are androgeno-insensitive [110] and may thus participate in the androgen-independent growth of prostate cancer. In addition, these cells are resistant to apoptosis [48] and secrete numerous factors that may increase cell proliferation in their vicinity.…”

Section: Ne Differentiation In Cancer Progression-perspectives On Thementioning

confidence: 99%

Expression and Role of T-type Calcium Channels during Neuroendocrine Differentiation

Warnier¹,

Gackière²,

Roudbaraki³

et al. 2017

J Cell Signal

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Neuroendocrine cells release their secretion into the extracellular environment through calcium-dependent signalling pathways. These cells share common morphological and molecular features such as the expression of specific biomarkers, neurite outgrowth and dense core secretory granules. In order to elucidate the signalling pathways leading from undifferentiated to differentiated neuroendocrine cells, the role of voltage-dependent calcium channels, central actors in the excitation-secretion coupling, has been comprehensively investigated. T-type calcium channels appear to belong to the most important ion channel family involved in the neuroendocrine differentiation process. They could also participate in the development of neuroendocrine tumours.

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“…The levels of serum CgA are increased in patients with prostate cancer compared with benign conditions. The early detection of high serum levels of CgA could be an indicator for a change to a more aggressive therapy [14] . Although the exact function of the NEF component is still unknown, it is evident that the NEF component in duodenal and other adenocarcinomas apparently has different functions.…”

Section: Peer-reviewmentioning

confidence: 99%

Endoscopic mucosal resection of duodenal bulb adenocarcinoma with neuroendocrine features: An extremely rare case report

Wen¹

2015

WJG

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Duodenal adenocarcinoma, especially duodenal bulb with neuroendocrine features (NEF), is extremely rare. Here, we report one such case of duodenal bulb adenocarcinoma with neuroendocrine features. A 63-year-old Han Chinese woman was admitted to our department with the diagnosis of a duodenal bulb polyp and underwent an endoscopic mucosal resection. The pathological findings confirmed it as duodenal bulb adenocarcinoma with NEF. The patient remains curative after one and half a years of follow-up. Duodenal adenocarcinoma with NEF might be a low malignant neuroendocrine tumor rather than a conventional adenocarcinoma. Endoscopic treatment, including endoscopic mucosal resection, might be an ideal option for the adenocarcinomas with NEF.

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Prognostic Significance of Neuroendocrine Differentiation in Prostate Adenocarcinoma

Cited by 39 publications

References 94 publications

Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells

Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells

Expression and Role of T-type Calcium Channels during Neuroendocrine Differentiation

Endoscopic mucosal resection of duodenal bulb adenocarcinoma with neuroendocrine features: An extremely rare case report

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