Osteoprotegerin and rank ligand expression in prostate cancer.
OBJECTIVE
To investigate the expression of osteoprotegerin (OPG) and RANK ligand (RANKL) in human prostatic tissues. The factors regulating the increased turnover associated with prostate cancer (CaP) bone metastasis are unknown. OPG and RANKL are recently identified regulators of bone resorption and bone remodeling.


METHODS
Tissues from 28 patients with CaP and from 4 normal organ donors were analyzed by reverse transcriptase-polymerase chain reaction and immunohistochemistry for the expression of OPG and RANKL.


RESULTS
OPG and RANKL messages were detected in both normal and cancerous prostate samples. In the normal prostate, OPG protein was detected in luminal epithelial and stromal cells (5% to 65% and 15% to 70%, respectively) and RANKL immunoreactivity was observed in 15% to 50% of basal epithelial cells, 40% to 90% of luminal epithelial cells, and 70% to 100% of stromal cells. OPG was not detected in 8 of 10 primary CaP specimens; RANKL was heterogeneously expressed in 10 of 11 CaP specimens. The percentage of tumor cells expressing OPG and RANKL was significantly increased in all CaP bone metastases compared with nonosseous metastases or primary CaP.


CONCLUSIONS
CaP bone metastases were consistently immunoreactive for both OPG and RANKL compared with nonosseous metastases or primary CaP. The presence of these crucial bone resorption regulators in CaP bone metastases suggests a mechanism whereby CaP cells may modulate bone turnover and has profound implications for the establishment and development of CaP bone metastases in advanced disease.
Brown
J M
JM
Department of Urology, University of Washington, Seattle, Washington, USA.
Corey
E
E
Lee
Z D
ZD
True
L D
LD
Yun
T J
TJ
Tondravi
M
M
Vessella
R L
RL
D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001859:Bone Neoplasms / Q000737:chemistry* / Q000556:secondary*; D002352:Carrier Proteins / Q000032:analysis*; D016207:Cytokines / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D053244:Osteoprotegerin; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000737:chemistry*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor
D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human