Endocrine and paracrine characteristics of neuroendocrine prostate cancer

Abstract

Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a spectrum of uncommon tumor types occur including those with small cell and neuroendocrine cell features. Benign neuroendocrine cells exist in the normal prostate microenvironment, and these cells may give rise to primary neuroendocrine carcinomas. However, the more common development of neuroendocrine prostate cancer is observed after therapeutics designed to repress the signaling program regulated by the androgen receptor which is active in the majority of localized and metastatic adenocarcinomas. Neuroendocrine tumors are identified through immunohistochemical staining for common markers including chromogranin A/B, synaptophysin and neuron specific enolase (NSE). These markers are also common to neuroendocrine tumors that arise in other tissues and organs such as the gastrointestinal tract, pancreas, lung and skin. Notably, neuroendocrine prostate cancer shares biochemical features with nerve cells, particularly functions involving the secretion of a variety of peptides and proteins. These secreted factors have the potential to exert local paracrine effects, and distant endocrine effects that may modulate tumor progression, invasion, and resistance to therapy. This review discusses the spectrum of factors derived from neuroendocrine prostate cancers and their potential to influence the pathophysiology of localized and metastatic prostate cancer.

Multifaceted impact of adipose conditioned media: Obesity‐driven promotion of prostate cancer and cancer stem cell dynamics

“…CXCR1 expression is higher in malignant cells compared to benign prostate tissue, potentially contributing to AR‐independent proliferation. NEPC cells express CXCR2, suggesting that IL‐8 might regulate NEPC cells and promote AR‐independent growth through an autocrine mechanism 47,48 . In our experiments, PC3 and LNCaP cells showed increased IL‐8 secretion due to ACM treatment, with CD44 + LNCaP PCSCs responding similarly (Figure 1C).…”

“…NEPC cells express CXCR2, suggesting that IL-8 might regulate NEPC cells and promote AR-independent growth through an autocrine mechanism. 47,48 In our experiments, PC3 and LNCaP cells showed increased IL-8 secretion due to ACM treatment, with CD44 + LNCaP PCSCs responding similarly (Figure 1C). This suggests that IL-8 from PC3 Limited data exists on ACM's direct impact on isolated PCSCs.…”

Genetically modified organisms in urological cancer

“…The model mice developed PIN at 8 weeks, followed by invasive cancer within 2-4 weeks and metastasis to lymph nodes, liver, lung, brain, and bone within 16 weeks [39]. The tumors were androgen-independent, recapitulating multiple histopathological features of human PCa while avoiding androgen dependence on neuroendocrine cancer evolution [40,41] [42,43]. This model recapitulates aspects of human PCa, with PIN observed around 10 weeks, progressing to invasive adenocarcinoma by 24 weeks and accompanied by distant metastases to lymph nodes, lungs, and liver [40].…”

MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

“…13,14 The function of these cells is not clear, but they might be playing a role in the differentiation and growth of the prostate cells by secreting neuropeptides like chromogranin A, serotonin, bombesin, cytokines and parathyroid hormone related proteins that induce the proliferation of adjacent cells through a paracrine mechanism. [15][16][17] NE cells are distinguished from other epithelial cells of the prostate by the lack of AR, and prostate specific antigen (PSA) and become resistant to AR inhibitors. 18 NE cells display structurally neuron like phenotypes and functionally endocrine like secretary mechanisms.…”