AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Transl Res 1(2):148-162;2009

Review Article
Neuroendocrine differentiation in prostate cancer

Yin Sun, Junyang Niu, Jiaoti Huang

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA;
Department of Pathology, Anhui Provincial Hospital, Hefei, Anhui Province, China.

Received February 2, 2009; accepted February 3, 2009; available online February 5, 2009

Abstract: As any organ in the body human prostate is composed of many different types of cells as well as
extracellular components. During prostate development, reciprocal cellular interactions between stromal cells
and prostate epithelial cells ultimately lead to the development of a mature prostate. Normal prostate is
composed of repeating cellular units that contain stromal and epithelial compartments. The epithelial
compartment contains luminal epithelial cells, basal cells and a minor component of neuroendocrine cells
whose function may be to regulate the growth, differentiation and secretory function of the prostate gland.
Neuroendocrine cells are also evident in prostate cancer and numerous studies showed that its number
increases in high grade and high stage tumors, particularly in hormonally treated and hormone-refractory
(androgen-independent) prostate cancer. Although androgen withdrawal reduces the secretion of the
andromedins from the prostate stromal cells that are critical for the survival for prostate epithelial cells, there is
clear evidence that androgen receptor is also required for the tumorigenesis of human prostate cancer, and
therefore androgen deprivation therapy likely works through inhibition of androgen receptor in the prostate
epithelium. Because neuroendocrine cells lack androgen receptor and are likely androgen-independent, it is
conceivable that hormonal therapy for advanced/metastatic prostate cancer, which consists of inhibiting androgen
production and/or blocking androgen receptor function, will not eliminate neuroendocrine cancer cells.  Instead,
these cells may be enriched after the therapy and they may establish paracrine networks to stimulate
androgen-independent proliferation of prostate cancer, leading to tumor recurrence. In this article, we will review
the known functions of the neuroendocrine cells in prostate cancer, including stimulation of cancer proliferation
and invasion, apoptosis resistance and angiogenesis as well as molecular pathways involved in neuroendocrine
differentiation. (AJTR902001).

Key Words: Prostate cancer, hormonal therapy, neuroendocrine

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Address all correspondence to:
Jiaoti Huang, MD, PhD,
Department of Pathology and Laboratory Medicine
David Geffen School of Medicine at UCLA
10833 Le Conte Ave., A7-149 CHS
Los Angeles, CA 90095-1732
Tel: 310-267-2264
Fax 310-267-2058