Expression of pleiotrophin in the prostate is androgen regulated and it functions as an autocrine regulator of mesenchyme and cancer associated fibroblasts and as a paracrine regulator of epithelia.
BACKGROUND
Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme have identified candidate molecules such as pleiotrophin (Ptn).


METHODS
Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR. Ptn function was examined by addition of hPTN protein to rat ventral prostate organ cultures, primary human fetal prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia.


RESULTS
During development, Ptn transcripts and protein were expressed in ventral mesenchymal pad (VMP) and prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal epithelial tips undergoing branching morphogenesis, and was located on the surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal and epithelial proliferation, when added to rat VP cultures, and also stimulated growth of fetal human prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice. Transcripts for PTN were upregulated by testosterone in fetal human prostate fibroblasts and organ cultures of female rat VMP. Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female.


CONCLUSIONS
Our data suggest that in the prostate Ptn functions as a regulator of both mesenchymal and epithelial proliferation, and that androgens regulate Ptn levels.
Orr
Brigid
B
MRC Human Reproductive Sciences Unit, The Queen's Medical Research Institute, Edinburgh, UK.
Vanpoucke
Griet
G
Grace
O Cathal
OC
Smith
Lee
L
Anderson
Richard A
RA
Riddick
Antony C P
AC
Franco
Omar E
OE
Hayward
Simon W
SW
Thomson
Axel A
AA
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D019899:Paracrine Communication; D011467:Prostate / Q000737:chemistry / Q000254:growth & development*; D011471:Prostatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology*; D014521:Urethra / Q000737:chemistry
D002352:Carrier Proteins; D016207:Cytokines; D012333:RNA, Messenger; D011944:Receptors, Androgen; C066845:pleiotrophin; D013739:Testosterone
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