Preprint Article Version 1 This version is not peer-reviewed

In Vitro Neuroendocrine Differentiation of BPH-1 Cells under β2 Adrenergic Receptor Stimulation

Version 1 : Received: 9 September 2024 / Approved: 10 September 2024 / Online: 10 September 2024 (15:10:26 CEST)

How to cite: Pigat, N.; Garrido Castillo, L. N.; Lefèvre, C.; Baures, M.; Goffin, V.; Anract, J.; Armand, A.-S.; Capiod, T. In Vitro Neuroendocrine Differentiation of BPH-1 Cells under β2 Adrenergic Receptor Stimulation. Preprints 2024, 2024090748. https://doi.org/10.20944/preprints202409.0748.v1 Pigat, N.; Garrido Castillo, L. N.; Lefèvre, C.; Baures, M.; Goffin, V.; Anract, J.; Armand, A.-S.; Capiod, T. In Vitro Neuroendocrine Differentiation of BPH-1 Cells under β2 Adrenergic Receptor Stimulation. Preprints 2024, 2024090748. https://doi.org/10.20944/preprints202409.0748.v1

Abstract

Objectives: Epidemiologic and experimental animal studies have shown that stress can alter tumor growth and that adrenergic fibers from the sympathetic nervous system, acting through stromal β2-adrenergic receptors, promote tumor cell survival during the initial phases of cancer development. Recent epidemiological data suggest that beta blocker intake improves survival of prostate cancer patients. Methods: Signaling mediated by β-adrenergic receptors promotes neuroendocrine differentiation in prostate cancer cell line. Although neuroendocrine cells are a minor population in the epithelial compartment of normal prostate glands, the population of neuroendocrine-like cells that express markers such as SYN, Bcl-2, Dll-3, and AMACR correlates with cancer progression, androgen-independent state, and poor prognosis in prostate cancer patients. As recent studies show that an increase in neuroendocrine cell density occurs before development of benign prostatic hyperplasia (BPH), a non-lethal disease affecting the transition zone, in hypertensive rats, we investigated whether neuroendocrine differentiation is associated with BPH. Results: Our results showed that isobutyl-methyl-xanthine and forskolin leading to sustained activation of the cAMP/PKA pathway led to an increase in neuroendocrine differentiation markers in BPH-1 cell line. Similar results were observed by combining the β-adrenergic receptors agonist isoproterenol with forskolin. These treatments reduced BPH-1 cell proliferation rates by 40% and 60%, respectively. Effects on neuroendocrine markers expression and cell proliferation were fully reversed by the β2 blocker carvedilol. Conclusion: These data suggest that β-adrenergic receptors are linked to the development of neuroendocrine-like cells in BPH. As 20% of the prostate cancer tumors occur in this zone, this observation warrants further investigation.

Keywords

beta blockers; prostate; AMACR; Synaptophysin; kscipline

Subject

Biology and Life Sciences, Life Sciences

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