Hedgehog pathway responsiveness correlates with the presence of primary cilia on prostate stromal cells.
BACKGROUND
Hedgehog (Hh) signaling from the urogenital sinus (UGS) epithelium to the surrounding mesenchyme plays a critical role in regulating ductal formation and growth during prostate development. The primary cilium, a feature of most interphase vertebrate cell types, serves as a required localization domain for Hh signaling transducing proteins.


RESULTS
Immunostaining revealed the presence of primary cilia in mesenchymal cells of the developing prostate. Cell-based assays of a urongenital sinus mesenchymal cell line (UGSM-2) revealed that proliferation-limiting (serum starvation and/or confluence) growth conditions promoted cilia formation and correlated with pathway activation associated with accumulation of Smoothened in primary cilia. The prostate cancer cell lines PC-3, LNCaP, and 22RV1, previously shown to lack demonstrable autocrine Hh signaling capacity, did not exhibit primary cilia even under proliferation-limiting growth conditions.


CONCLUSIONS
We conclude that paracrine Hedgehog signaling activity in the prostate is associated with the presence of primary cilia on stromal cells but that a role in autocrine Hh signaling remains speculative.
Zhang
Jingxian
J
Department of Urology, University of Wisconsin-Madison, Madison, WI, USA. jingxian99@yahoo.com
Lipinski
Robert J
RJ
Gipp
Jerry J
JJ
Shaw
Aubie K
AK
Bushman
Wade
W
D002460:Cell Line; D002923:Cilia / Q000648:ultrastructure*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000378:metabolism* / Q000648:ultrastructure*; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism* / Q000648:ultrastructure
D053823:Hedgehog Proteins