Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists

Muñoz-Moreno, Laura; Carmena, Marı́a J.; Prieto, Juan Carlos; Bajo, Ana M.

doi:10.1007/s10637-019-00831-2

Cited by 14 publications

(10 citation statements)

References 23 publications

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“…The exposure of RWPE‐1 cells to GHRH results in tumorigenic transformation since these cells acquire characteristics in common with human PCa cells including hyperproliferative activity, increased gelatinolytic activity of MMP‐2, decreased cell adhesion and increased cell migration. In this regard, GHRH receptor antagonists have been reported to block the effects of GHRH 15,27,28 . All this together corroborates the important role of GHRH as a mediator in the initiation and progression of PCa.…”

Section: Discussionsupporting

confidence: 70%

“…The most important sources of nonhypothalamic GHRH production is found in various tumors and their cell lines 13 . GHRH promotes metastatic phenotypes in both androgen‐responsive (lymph node carcinoma of the prostate [LNCaP]) and androgen‐unresponsive (PC3) prostate adenocarcinoma cell lines 14 and stimulates neuroendocrine differentiation in LNCaP 15 . Taken together, these results support the important role of GHRH in tumor establishment and progression in prostate cells.…”

Section: Introductionsupporting

confidence: 52%

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Tumorigenic transformation of human prostatic epithelial cell line RWPE‐1 by growth hormone‐releasing hormone (GHRH)

et al. 2022

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Background: Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In this study, we analyzed the carcinogenetic potential of exposure to GHRH of a nontumor human prostate epithelial cell line (RWPE-1) as well as its transforming effect in a xenograft model. Methods: We performed cell viability, cell proliferation, adhesion and migration assays. In addition, metalloprotease (MMP)−2 activity by means gelatin zymography, GHRH-R subcellular location using confocal immunofluorescence microscopy and vascular endothelial growth factor (VEGF) levels by enzyme-linked immunoassay were assessed. Besides, we developed an in vivo model in order vivo model to determine the role of GHRH on tumorigenic transformation of RWPE-1 cells. Results: In cell cultures, we observed development of a migratory phenotype consistent with the gelatinolytic activity of MMP-2, expression of VEGF, as well as E-cadherin-mediated cell-cell adhesion and increased cell motility. Treatment with 0.1 µM GHRH for 24 h significantly increased cell viability and cell proliferation. Similar effects of GHRH were seen in RWPE-1 tumors developed by subcutaneous injection of GHRH-treated cells in athymic nude mice, 49 days after inoculation.Conclusions: Thus, GHRH appears to act as a cytokine in the transformation of RWPE-1 cells by mechanisms that likely involve epithelial-mesenchymal transition, thus reinforcing the role of GHRH in tumorigenesis of prostate.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionsupporting

confidence: 52%

Tumorigenic transformation of human prostatic epithelial cell line RWPE‐1 by growth hormone‐releasing hormone (GHRH)

et al. 2022

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“…The release of Growth Hormone (GH) is regulated by the hypothalamic Growth Hormone Releasing Hormone (GHRH) [ 3 , 36 ]. It was recently shown that GHRH antagonists induce both UPR and P53 [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Heat Shock Protein 90 Inhibition In the Lungs

Uddin

Kubra

Sonju

et al. 2020

Medicine in Drug Discovery

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Inhibition of Hsp90 is associated with anti-inflammatory effects. We employed human lung microvascular endothelial cells to investigate the effects of the Hsp90 inhibitors 17-AAG, AUY-922 and 17-DMAG in the unfolded protein response (UPR) and viability of lung cells. Our observations indicate that moderate doses of those compounds trigger the activation of the UPR without inducing lethal effects in vitro . Indeed, AUY-922 triggered UPR activation in the lungs of C57BL/6 mice. UPR has been previously involved in the enhancement of the lung endothelial barrier function. Thus, the present study suggests that the barrier protective effects of Hsp90 inhibition in the lung microvasculature are highly probable to be associated with the activation of the UPR. Hence, the development of novel compounds which stochastically capacitate the repairing elements of UPR, may deliver new therapeutic possibilities against the severities of the acute respiratory distress syndrome.

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“…NED is a complex progression in which cellular reprogramming and epigenetic modulation are involved [ 14 , 91 , 92 ]. EGFR signaling induces NED via the following actions: repressing AR expression and initiating ENO2 expression, which are activated by GABAAR, heparin-binding EGF-like growth factor (HB-EGF), PTHrP autocrine/paracrine; or growth hormone-releasing hormone (GHRH)-mediated calcium flux [ 63 , 93 , 94 , 95 , 96 , 97 , 98 ] ( Figure 8 ). Interestingly, Martin-Orozco et al reported that EGFR-mediated NED is activated via the PI3K/AKT/ERK cascade.…”

Section: Egfr Signalingmentioning

confidence: 99%

Interplay of Epidermal Growth Factor Receptor and Signal Transducer and Activator of Transcription 3 in Prostate Cancer: Beyond Androgen Receptor Transactivation

Lin

Yeh

Liu

2021

Cancers

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Prostate cancer (PCa) is one of the most common cancers in the world and causes thousands of deaths every year. Conventional therapy for PCa includes surgery and androgen deprivation therapy (ADT). However, about 10–20% of all PCa cases relapse; there is also the further development of castration resistant adenocarcinoma (CRPC-Adeno) or neuroendocrine (NE) PCa (CRPC-NE). Due to their androgen-insensitive properties, both CRPC-Adeno and CRPC-NE have limited therapeutic options. Accordingly, this study reveals the inductive mechanisms of CRPC (for both CRPC-Adeno and CRPC-NE) and fulfils an urgent need for the treatment of PCa patients. Although previous studies have illustrated the emerging roles of epidermal growth factor receptors (EGFR), signal transducer, and activator of transcription 3 (STAT3) signaling in the development of CRPC, the regulatory mechanisms of this interaction between EGFR and STAT3 is still unclear. Our recent studies have shown that crosstalk between EGFR and STAT3 is critical for NE differentiation of PCa. In this review, we have collected recent findings with regard to the involvement of EGFR and STAT3 in malignancy progression and discussed their interactions during the development of therapeutic resistance for PCa.

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Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists

Cited by 14 publications

References 23 publications

Tumorigenic transformation of human prostatic epithelial cell line RWPE‐1 by growth hormone‐releasing hormone (GHRH)

Tumorigenic transformation of human prostatic epithelial cell line RWPE‐1 by growth hormone‐releasing hormone (GHRH)

Effects of Heat Shock Protein 90 Inhibition In the Lungs

Interplay of Epidermal Growth Factor Receptor and Signal Transducer and Activator of Transcription 3 in Prostate Cancer: Beyond Androgen Receptor Transactivation

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