Neuroendocrine Differentiation in Prostate Cancer: From Lab to Bedside

Cindolo, Luca; Cantile, Monica; Vacherot, Francis; Terry, Stéphane; Taille, Alexandre de la

doi:10.1159/000109711

Cited by 41 publications

(36 citation statements)

References 151 publications

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“…Interestingly, the βIII-tubulin-overexpressing LNCaP cells had a neuroendocrine-like appearance (Supplementary Fig. S3), suggesting that forced expression of βIII-tubulin is associated with a transdifferentiation process that has been frequently described for these cells (31,32). To examine the effects of βIII-tubulin overexpression, we measured the half-time inhibitory concentration (IC 50 ) of docetaxel assessed by measuring cell viability at 72 hours after exposure.…”

Section: Stable Overexpression Of βIii-tubulin In Pca Cell Lines Confmentioning

confidence: 98%

Class III β-Tubulin Expression Predicts Prostate Tumor Aggressiveness and Patient Response to Docetaxel-Based Chemotherapy

et al. 2010

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Expression of class III β-tubulin (βIII-tubulin) correlates with tumor progression and resistance to taxanebased therapies for several human malignancies, but its use as a biomarker of tumor behavior in prostate cancer (PCa) remains largely unexplored. Here, we describe βIII-tubulin immunohistochemical staining patterns of prostate tumors obtained from a broad spectrum of PCa patients, some of whom subsequently received docetaxel therapy for castration-resistant PCa (CRPC). Elevated βIII-tubulin expression was significantly associated with tumor aggressiveness in PCa patients with presumed localized disease, as it was found to be an independent marker of biochemical recurrence after treatment. Additionally, βIII-tubulin expression in tumor cells was an independent predictor of lower overall survival for patients receiving docetaxel-based chemotherapy for CRPC. Manipulation of βIII-tubulin expression in human PCa cell lines using a human βIII-tubulin expression vector or βIII-tubulin small interfering RNA altered cell survival in response to docetaxel treatment in a manner that supports a role for βIII-tubulin expression as a mediator of PCa cell resistance to docetaxel therapy. Our findings suggest a role for βIII-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC.

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Section: Stable Overexpression Of βIii-tubulin In Pca Cell Lines Confmentioning

confidence: 98%

Class III β-Tubulin Expression Predicts Prostate Tumor Aggressiveness and Patient Response to Docetaxel-Based Chemotherapy

et al. 2010

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“…T h e w e l l -d o c u m e n t e d c o r r e l a t i o n s (18,23,25,26) between the Ki-67 expression and the aggressive features of PCa were confirmed here by the demonstration of its significant association with Gleason score, ChrA expression and survival. On the other hand, the absence of correlation with the NeuroD1 and AR (Figure-2) could be explained by the fact that Ki-67 is only a marker of proliferation, whereas NeuroD1 and AR are implicated into the neuroendocrine differentiation pathway (9,14,27,28).…”

Section: Commentsmentioning

confidence: 99%

“…Further experiments are needed to demonstrate that for the early detection of NE activity an integrated diagnostic panel (e.g. Dopa-Decarboxylase, a-methylacyl-CoA racemase, IL-8 receptors) should be proposed (9).…”

Section: Commentsmentioning

confidence: 99%

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Parallel determination of NeuroD1, Chromogranin-A, KI67 and androgen receptor expression in surgically treated prostate cancers

Cindolo¹,

Cantile

Franco

et al. 2011

Int. braz j urol.

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Purpose: Neuroendocrine differentiation is a hallmark of prostate cancer. The aim of our study was the detection of the parallel expression of neuroendocrine related markers using a prostate tissue microarray (TMA). Materials and Methods: Our study was aimed at detecting the parallel expression of NeuroD1, Chromogranin-A (ChrA), Androgen Receptor (AR) and Ki-67 by immunohistochemistry on prostate cancer tissue microarray. The data was analyzed using SAS version 8.2 (SAS Inc, Cary, NC). The relationships between NeuroD1, ChrA and AR expressions and patients' characteristics were investigated by multivariate logistic regression analysis. Progression and Overall Survival (OS) distributions were calculated using Kaplan-Meier method. Results: Tissue reactivity for NeuroD1, ChrA and AR concerned 73%, 49% and 77% of the available cases, respectively. Regarding overall survival, there were 87 deaths and 295 patients alive/censored (6 years of median follow-up). Seventyseven disease progressions occurred at the median follow-up 5.4y. A significant correlation between NeuroD1, ChrA and AR expression was observed (p < 0.001 and p < 0.03, respectively). Additionally, ChrA was strongly associated in multivariate analysis to Gleason score and Ki67 expression (p < 0.009 and p < 0.0052, respectively). Survival analysis showed no association between markers neither for overall nor for cancer-specific survival. Conclusions:The results highlight that NeuroD1, Chromogranin-A and Androgen Receptor are strongly associated, however their expression does not correlate with overall survival or disease progression.

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“…3 Yet, research efforts during the last 50 years have not improved significantly the life expectancy of PCa patients. 4 Adult prostate gland possesses basal (proliferating) cells, secretory (luminal) cells and the less abundant (<0.1%) neuroendocrine (NE) cells. NE cells, included in the diffuse endocrine system, share common features with neurons and are present at all the stages from normal benign to prostate adenocarcinomas.…”

mentioning

confidence: 99%

Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells

Quiros

Sáinz

Hevia

et al. 2009

Intl Journal of Cancer

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Despite improvements in diagnosis of advanced prostate cancer (PCa), treatment is not efficient and 5-year survival is still low. Initially, the less abundant of cell types, neuroendocrine cells (NE), are involved in regulatory process but their physiological role is not fully understood. Among others, an increase in NE cells along with tumor progression has been commonly reported but their role in tumorigenesis or the molecular mechanisms of transdifferentiation is still a matter of debate. We have used human PCa cells (LNCaP) induced to differentiate to NE cells with several stimuli: androgen withdrawal, cyclic AMP or treatment with the antioxidant pineal hormone melatonin. PCa patients' specimens were also analyzed by western blotting and by immunocytochemistry. NE-like LNCaP cells express high levels of mitochondrial superoxide dismutase (MnSOD/SOD2) in addition to NE markers. MnSOD upregulation is mediated by NFjB transcription factor, mainly through p65 translocation into the nuclei. More importantly, overexpression of MnSOD induces the rise of NE-markers in LNCaP cells, showing that MnSOD upregulation might be instrumental for NE differentiation in PCa cells. Furthermore, MnSOD is highly expressed in advanced tumors of patients' when compared with control, nonpathological samples or with low-grade tumors, along with the presence of synaptophysin, a common NE marker. Also, fluorescence immunohistochemical analysis revealed that MnSOD colocalizes with NE markers in most of NE cells observed in PCa specimens. The present findings indicate that MnSOD is essential for NE transdifferentiation and mediates in part the differentiation process, which appears also to be critical in vivo. ' 2009 UICC

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Neuroendocrine Differentiation in Prostate Cancer: From Lab to Bedside

Cited by 41 publications

References 151 publications

Class III β-Tubulin Expression Predicts Prostate Tumor Aggressiveness and Patient Response to Docetaxel-Based Chemotherapy

Class III β-Tubulin Expression Predicts Prostate Tumor Aggressiveness and Patient Response to Docetaxel-Based Chemotherapy

Parallel determination of NeuroD1, Chromogranin-A, KI67 and androgen receptor expression in surgically treated prostate cancers

Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells

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