The neuropeptide 26RFa is expressed in human prostate cancer and stimulates the neuroendocrine differentiation and the migration of androgeno-independent prostate cancer cells

Jessy Alonzeau (1) , David Alexandre (1) , Lydie Jeandel (1) , Maïté Courel (1) , Coralie Hautot (1) , Fatima-Zohra El Yamani (2) , Françoise Gobet (3) , Jérô Me Leprince (1) , Rabia Magoul , Afaf Amarti (4) , Christian Pfister (5) , Laurent Yon (1) , Youssef Anouar (1) , Nicolas Chartrel (1)

1 DC2N - Différenciation et communication neuronale et neuroendocrine
2 USMBA - Université Sidi Mohamed Ben Abdellah
3 CHU Rouen
4 CHU HII - Centre Hospitalier Universitaire Hassan II
5 Service d'urologie [Rouen]

Aim: Accumulating data suggest that neuropeptides produced by neuroendocrine cells play a crucial role in the progression and aggressiveness of hormone refractory prostate cancer (CaP). In this study, we have investigated the presence and function of the neuropep-tide 26RFa in CaP. Methods: We have localised and quantified tumour cells containing 26RFa and its receptor, GPR103, in CaP sections of various grades. In vitro experiments were performed to investigate the effects of 26RFa on the migration, proliferation and neuroendocrine differentiation of the androgeno-independent (AI) prostate cancer cell line DU145. Results: 26RFa and GPR103 are present in carcinomatous foci exhibiting a neuroendocrine differentiation, and the number of 26RFa and GPR103-immunoreactive cancer cells increases with the grade of CaP. 26RFa stimulated the migration of native or transdifferentiated AI DU145 cells, but had no effect on their proliferation. Furthermore, 26RFa induced the neu-roendocrine differentiation of DU145 cells as assessed by the occurrence of neurite-like extensions and the increase of the expression of the neuroendocrine marker chromogranin A. Conclusion: The present data indicate that 26RFa may participate to the development of CaP at the AI state by promoting the neuroendocrine differentiation and the migration of cancer cells via autocrine/paracrine mechanisms.

Mots clés: Neuropeptide; Neuroendocrine differentiation; G protein-coupled receptor; Advanced prostate cancer

Domaines: Cancer; Urologie et Néphrologie

Jessy Alonzeau, David Alexandre, Lydie Jeandel, Maïté Courel, Coralie Hautot, et al.. The neuropeptide 26RFa is expressed in human prostate cancer and stimulates the neuroendocrine differentiation and the migration of androgeno-independent prostate cancer cells. European Journal of Cancer, 2013, 49 (2), pp.511-519. ⟨10.1016/j.ejca.2012.05.028⟩. ⟨hal-01706422⟩