Monitoring of skeletal progression of prostate cancer by GFP imaging, X-ray, and serum OPG and PTHrP.
BACKGROUND
Prostate cancers (PCas) produce factors that can serve as biomarkers for tumor metastasis and bone progression. Transduced GFP expression by cancer cells can be imaged to monitor therapy. We exploited both concepts by developing a GFP-expressing PCa cell line that expresses PTHrP and studying it in an animal model of malignancy with methods that assess the skeletal progression of this tumor.


METHODS
We developed a GFP-producing PCa cell line by stable transduction of PC-3 PCa cells. This PC-3 variant was used to study tumor progression in an immunocompromised mouse model. Skeletal progression of the PCa cells and the effects of pamidronate administration were evaluated radiologically, fluorometrically, and by measurement of serum tumor markers.


RESULTS
The PC-3 cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3 cells could be monitored by GFP optical imaging, X-ray, and by measurements of tumor products in serum, notably PTHrP and OPG. Pamidronate treatment reduced tumor burden as assessed at autopsy by imaging and biomarkers.


CONCLUSIONS
Pamidronate treatment exhibited anti-tumor effects that were reflected by decreases in serum PTHrP, OPG, and by GFP and radiological imaging procedures. Imaging of GFP expression enables real-time monitoring of tumor growth in the bone. PTHrP and OPG may be useful as tumor biomarkers for PCa that has metastasized to bone. This novel human PCa model can be used to study the clinical potential of diagnostic and therapeutic modalities in the skeletal progression of PCas.
Burton
D W
DW
Department of Medicine, University of California and San Diego Veterans Administration Healthcare System (VASDHS), San Diego, California 92161, USA.
Geller
J
J
Yang
M
M
Jiang
P
P
Barken
I
I
Hastings
R H
RH
Hoffman
R M
RM
Deftos
L J
LJ
D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism / Q000556:secondary*; D002118:Calcium / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000097:blood*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D053244:Osteoprotegerin; D000077268:Pamidronate; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D053245:RANK Ligand; D011859:Radiography; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D014161:Transduction, Genetic
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004164:Diphosphonates; D006023:Glycoproteins; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein; D053245:RANK Ligand; 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; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D049452:Green Fluorescent Proteins; D000077268:Pamidronate; D002118:Calcium