Proximal prostate stem cells are programmed to regenerate a proximal-distal ductal axis

¹ Department of Cell Biology, New York University, School of Medicine, New York, New York; Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
² Department of Cell Biology, New York University School of Medicine, New York, New York; Department of Science, Borough of Manhattan Community College, New York, New York
³ Department of Cell Biology, New York University School of Medicine, New York, New York
⁴ Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
⁵ Department of Urology, New York University School of Medicine, New York, New York
⁶ Department of Cell Biology, New York University School of Medicine, New York, New York; Kaplan Cancer Center, New York University School of Medicine, New York, New York
⁷ Department of Cell Biology, New York University School of Medicine, New York, New York; Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Kaplan Cancer Center, New York University School of Medicine, New York, New York; Department of Urology, New York University School of Medicine, New York, New York

^* To whom correspondence should be addressed. E-mail: wilsoe01{at}popmail.med.nyu.edu.

	Abstract

Prostate carcinoma and benign prostatic hypertrophy may both originate in stem cells, highlighting the importance of the characterization of these cells. The prostate gland contains a network of ducts each of which consists of a proximal (adjacent to the urethra), an intermediate and a distal region. Here we report that two populations of cells capable of regenerating prostatic tissue in an in vivo prostate reconstitution assay are present in different regions of prostatic ducts. The first population (with considerable growth potential) resides in the proximal region of ducts and in the urethra and the survival of these cells does not require the presence of androgens. The second population (with more limited growth potential) is found in the remaining ductal regions and requires androgen for survival. In addition, we find that primitive proximal prostate cells, that are able to regenerate functional prostatic tissue in vivo, are also programmed to re-establish a proximal-distal ductal axis. Similar to their localization in the intact prostate, cells with the highest regenerative capacity are found in the proximal region of prostatic ducts formed in an in vivo prostate reconstitution assay. The primitive proximal cells can be passaged through four generations of sub-renal capsule grafts. Together, these novel findings illustrate features of primitive prostate cells that may have implications for the development of therapies for treating proliferative prostatic diseases.

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