Osteoprotegerin is expressed in colon carcinoma cells.
BACKGROUND
Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor family, is produced by various cell types and tissues and plays a key role in the physiological regulation of osteoclast differentiation and activity. Also, OPG is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing factor (TRAIL). In the present study we investigated whether the human colon cancer cell lines HT-29 and SW-480 produce and secrete OPG in vitro.


METHODS
Expression of OPG mRNA was examined by RT-PCR. OPG protein was analysed by ELISA assay and immunostaining methods. The effect of OPG secretion on TRAIL-mediated apoptosis was also investigated.


RESULTS
By RT-PCR, it was demonstrated that mRNA transcripts for OPG were produced by both cell lines. By ELISA analysis, OPG was detected in the culture medium; and treatment of cells with proinflammatory cytokines TNF-alpha and IL-1beta increased OPG secretion significantly. Tumor xenografts in nude mice also were shown to express OPG by immunohistochemistry. When RANKL, which selectively binds OPG, was added to cell cultures along with recombinant TRAIL, apoptosis was shown to increase significantly.


CONCLUSIONS
These data indicate that OPG may be involved in tumorigenesis and the progression of colon cancer.
Pettersen
Ingvild
I
Department of Experimental Pathology, Medical Faculty, University of Tromsø, N-9037, Tromsø, Norway.
Bakkelund
Wenche
W
Smedsrød
Bård
B
Sveinbjørnsson
Baldur
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D007375:Interleukin-1; 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; D053221:TNF-Related Apoptosis-Inducing Ligand; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505653:TNFSF10 protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505654:Tnfsf10 protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha