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Investigational New Drugs

Erschienen in:

17.07.2019 | PRECLINICAL STUDIES

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

verfasst von: Laura Muñoz-Moreno, María J. Carmena, Andrew V. Schally, Juan C. Prieto, Ana M. Bajo

Erschienen in: Investigational New Drugs | Ausgabe 3/2020

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Summary

Prostate cancer is the second leading cause of cancer-related deaths among men in developed countries. Neuroendocrine prostate cancer, in particular, is associated with an aggressive phenotype and a poor prognosis. Neuroendocrine cells produce and secrete peptide hormones and growth factors in a paracrine/autocrine manner which promote the progression of the disease. Recent studies have demonstrated that extracellular vesicles or exosomes are released by prostate cancer cells, supporting the spread of prostate cancer. Hence, the aim of this study was to investigate the effect of growth hormone-releasing hormone (GHRH) on neuroendocrine differentiation (NED) in the androgen-dependent prostate cancer cell line LNCaP and the molecular mechanisms underlying these effects. GHRH induced an increase in the percentage of neurite-bearing cells and in the protein levels of Neuron-Specific Enolase. Both effects were blocked by the GHRH receptor antagonist MIA-690. In addition, pretreatment of these cells with the calcium chelator BAPTA, the EGFR inhibitor AG-1478 or the HER2 inhibitor AG-825 reduced the effect of GHRH, suggesting that the GHRH-induced stimulation of NED involves calcium channel activation and EGFR/HER2 transactivation. Finally, PC3-derived exosomes led to an increase in NED, cell proliferation and cell adhesion. Altogether, these findings suggest that GHRH antagonists should be considered for in the management of neuroendocrine prostate cancer.

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Titel: Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists
verfasst von: Laura Muñoz-Moreno
María J. Carmena
Andrew V. Schally
Juan C. Prieto
Ana M. Bajo
Publikationsdatum: 17.07.2019
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 3/2020
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00831-2

Springer Medizin

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

Summary

Neu im Fachgebiet Onkologie

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Update Onkologie

Springer Medizin

Summary

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