Proximal prostatic stem cells are programmed to regenerate a proximal-distal ductal axis.
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 subrenal 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.
Goto
Ken
K
Department of Cell Biology, MSB 634, NYU School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Salm
Sarah N
SN
Coetzee
Sandra
S
Xiong
Xiaozhong
X
Burger
Patricia E
PE
Shapiro
Ellen
E
Lepor
Herbert
H
Moscatelli
David
D
Wilson
E Lynette
EL
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D008954:Models, Biological; D011467:Prostate / Q000166:cytology* / Q000254:growth & development*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013370:Subrenal Capsule Assay
D000728:Androgens