Neuroendocrine differentiation of prostate cancer

Li, Zhen; Chen, Clark J; Wang, Jason K.; Hsia, Elaine; Li, Wei; Squires, Jill; Sun, Yin; Huang, Jiaoti

doi:10.1038/aja.2013.7

Cited by 35 publications

(33 citation statements)

References 30 publications

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“…The mechanisms why targeting androgen/AR signals leads to increase the NE differentiation in PCa remain unclear. Li et al found IL8-CXCR5-P53 signal is involved in the NE differentiation (Li et al, 2013), and Park et al found P21 may function through PAK4 to promote NE differentiation (Park et al, 2012). Our finding of the potential involvement of miRNAs , especially the miRNA-32 and miRNA-let7a, suggest that targeting this newly identified AR-miRNA32 signal may allow us to develop a better therapy to suppress the NE differentiation-induced PCa cell invasion.…”

Section: Discussionmentioning

confidence: 55%

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Anti‐androgen enzalutamide enhances prostate cancer neuroendocrine (NE) differentiation via altering the infiltrated mast cells → androgen receptor (AR) → miRNA32 signals

Dang

Xie

et al. 2015

Molecular Oncology

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The recently developed anti-androgen enzalutamide also known as (MDV3100) has the advantage to prolong by 4.8 months the survival of castration resistant prostate cancer (CRPC) patients. However, the mechanisms behind the potential side effects involving the induction of the prostate cancer (PCa) neuroendocrine (NE) differentiation remain unclear. Here we found PCa cells could recruit more mast cells than normal prostate epithelial cells, and enzalutamide (or casodex) treatment could further increase such recruitment that resulted in promoting the PCa NE differentiation. Mechanism dissection found infiltrated mast cells could function through positive feedback to enhance PCa to recruit more mast cells via modulation of the androgen receptor (AR) → cytokines IL8 signals, and interruption by AR-siRNA or neutralizing anti-IL8 antibody could partially reverse the recruitment of mast cells. Importantly, targeting the PCa androgens/AR signals with AR-siRNA or enzalutamide (or casodex) also increased PCa NE differentiation via modulation of the miRNA32 expression, and adding miRNA32 inhibitor reversed the AR-siRNA- or enzalutamide-enhanced NE differentiation. Together, these results not only identified a new signal via infiltrated mast cells → PCa AR → miRNA32 to increase PCa NE differentiation, it also pointed out the potential unwanted side effects of enzalutamide (or casodex) to increase PCa NE differentiation. Targeting these newly identified signals, including AR, IL8, or miRNA32, may help us to better suppress PCa NE differentiation that is induced during ADT with anti-androgen enzalutamide (or casodex) treatment.

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Section: Discussionmentioning

confidence: 55%

“…Li et al. found IL8‐CXCR5‐P53 signal is involved in the NE differentiation (Li et al., 2013), and Park et al. found P21 may function through PAK4 to promote NE differentiation (Park et al., 2012).…”

Section: Discussionmentioning

confidence: 99%

Anti‐androgen enzalutamide enhances prostate cancer neuroendocrine (NE) differentiation via altering the infiltrated mast cells → androgen receptor (AR) → miRNA32 signals

Dang

Xie

et al. 2015

Molecular Oncology

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“…Androgen blockade can induce NE differentiation. As NE cells do not express AR, they survive and proliferate under androgen deprivation . Therapy‐induced NE differentiation is associated with a poor response to AR‐targeted treatments and prognosis …”

Section: Discussionmentioning

confidence: 99%

Cutaneous metastases from prostate cancer revealing neuroendocrine differentiation

et al. 2019

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“…CXCR1 is overexpressed in PCa cells, and it has been hypothesized that paracrine activation of CXCR1 by IL-8 may contribute to androgen-independent proliferation of prostate cancer in patients treated with ADT [61]. Moreover, NE cells express IL-8 and CXCR2, as observed by staining serial sections of PCa tissue [64]. Notably, G31P, a CXCR1/2 inhibitor, has been shown to inhibit prostate cancer cell growth in vitro and in nude mouse xenografts [58].…”

Section: Interleukin-8 and Macrophage Migration Inhibitory Factormentioning

confidence: 94%

Neuroendocrine differentiation in prostate cancer: Novel morphological insights and future therapeutic perspectives

Santoni

Conti

Burattini

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Neuroendocrine differentiation of prostate cancer

Cited by 35 publications

References 30 publications

Anti‐androgen enzalutamide enhances prostate cancer neuroendocrine (NE) differentiation via altering the infiltrated mast cells → androgen receptor (AR) → miRNA32 signals

Anti‐androgen enzalutamide enhances prostate cancer neuroendocrine (NE) differentiation via altering the infiltrated mast cells → androgen receptor (AR) → miRNA32 signals

Cutaneous metastases from prostate cancer revealing neuroendocrine differentiation

Neuroendocrine differentiation in prostate cancer: Novel morphological insights and future therapeutic perspectives

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