Secretogranin II is overexpressed in advanced prostate cancer and promotes the neuroendocrine differentiation of prostate cancer cells

Maïté Courel (1) , Fatima-Zohra El Yamani (1) , David Alexandre (1) , Hinde El Fatemi (1) , Charlène Delestre (1) , Maite Montero-Hadjadje (1) , Fadl Tazi , Afaf Amarti , Rabia Magoul , Nicolas Chartrel (1) , Youssef Anouar (1)

1 DC2N - Différenciation et communication neuronale et neuroendocrine

Aim In prostate cancer (PCa), neuroendocrine differentiation (NED) is commonly observed in relapsing, hormone therapy-resistant tumours after androgen deprivation. However, the molecular mechanisms involved in the NED of PCa cells remain poorly understood. In this study, we investigated the expression of the neuroendocrine secretory protein secretogranin II (SgII) in PCa, and its potential involvement in the progression of this cancer as a granulogenic factor promoting NED. Methods We have examined SgII immunoreactivity in 25 benign prostate hyperplasia and 32 PCa biopsies. In vitro experiments were performed to investigate the involvement of SgII in the neuroendocrine differentiation and the proliferation of PCa cell lines. Results We showed that immunoreactive SgII intensity correlates with tumour grade in PCa patients. Using the androgen-dependent lymph node cancer prostate cells (LNCaP) cells, we found that NED triggered by androgen deprivation is associated with the induction of SgII expression. In addition, forced expression of SgII in LNCaP cells implemented a regulated secretory pathway by triggering the formation of secretory granule-like structures competent for hormone storage and regulated release. Finally, we found that SgII promotes prostate cancer (CaP) cell proliferation. Conclusion The present data show that SgII is highly expressed in advanced PCa and may contribute to the neuroendocrine differentiation by promoting the formation of secretory granules and the proliferation of PCa cells.

Keywords: Secretogranin, Secretory granule, Neuroendocrine differentiation, Prostate cancer

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Cellular Biology; Life Sciences [q-bio]; Cellular Biology; Cell Behavior [q-bio.CB]; Life Sciences [q-bio]; Cancer; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Biochemistry [q-bio.BM]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Molecular biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Molecular Networks [q-bio.MN]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Genomics [q-bio.GN]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Biophysics; Life Sciences [q-bio]; Cellular Biology; Subcellular Processes [q-bio.SC]

Maïté Courel, Fatima-Zohra El Yamani, David Alexandre, Hinde El Fatemi, Charlène Delestre, et al.. Secretogranin II is overexpressed in advanced prostate cancer and promotes the neuroendocrine differentiation of prostate cancer cells. European Journal of Cancer, 2014, 50 (17), pp.3039-3049. ⟨10.1016/j.ejca.2014.09.009⟩. ⟨hal-02341807⟩