AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation
Plenary Session

AB007. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation

Shimiao Zhu, Zhiqun Shang, Hao Tian, Amilcar Flores-Morales, Yuanjie Niu

Tianjin Institute of Urology & Department of Urology, Second Hospital of Tianjin Medical University, Tianjin 300211, China


Abstract: The mechanism of neuroendocrine transdifferentiation (NED) during the development of castration-resistant prostate cancer (CRPC) remains undefined. Although androgen-deprivation therapy (ADT) can impair tumor cell growth, ADT can also triggers a parallel reaction, leading to increased neurotensin (NTS) production in cancer associated stromal cells which drives NED. Here, we systematically explore the NTS network in tumor microenvironment that drives NED following ADT. The CK8+/CK14+ intermediate cells, as opposed to other epithelial cells, can be transdifferentiated to neuroendocrine (NE) status by excessive NTS through simultaneous activation of neurotensin receptor 1 (NTSR1)-PRKACB and 3 (NTSR3)-AHNAK axes. The importance of PRKACB and AHNAK in NED development was then confirmed in human prostate tumor tissues. More importantly, we demonstrated SR48692 (an inhibitor of NTSR1) could inhibit NED and prevent castration resistance in prostate tumor from xenografts and TRAMP models. We propose that targeting this pathway could provide benefit for patients with tumors expressing high levels of NTS following ADT.

Keywords: Neuroendocrine transdifferentiation; castration-resistant prostate cancer; androgen-deprivation therapy


doi: 10.21037/tau.2016.s007


Cite this abstract as: Zhu S, Shang Z, Tian H, Flores-Morales A, Niu Y. Neurotensin derived from cancer stroma contributes to castration resistance via promoting neuroendocrine transdifferentiation. Transl Androl Urol 2016;5(Suppl 1):AB007. doi: 10.21037/tau.2016.s007

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