Non-invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model.
BACKGROUND
We previously established a bioluminescent transgenic mouse model, sPSA-Luc, with luciferase gene expression restricted to the prostate under the control of the supra prostate-specific antigen (sPSA) promoter. We now assess the feasibility of generating bigenic mice, TRAMP-Luc, with the sPSA-Luc as the founder strain crossbred with TRAMP (transgenic adenocarcinoma mouse prostate) mice, to evaluate non-invasively the metastatic potential of prostate tumors.


METHODS
TRAMP-Luc mice were obtained as [C57BL/6 TRAMP x FVB sPSA-Luc] F1 offspring. Tumor development in 10 TRAMP-Luc males was followed by bioluminescence imaging from 8 to 24 weeks of age. Immunohistochemical (IHC) staining for T antigen (Tg), androgen receptor (AR), luciferase and/or pathological analysis verified the tumor distribution in the imaged tissues including prostate gland, lymph node and bone.


RESULTS
Group I animals that presented with no grossly visible tumors showed prostate-confined bioluminescence with slightly increased signal intensity with age. Group II animals that developed large tumors displayed a widely distributed and biphasic bioluminescence pattern. The peak was reached between 10 and 14 weeks of age, then markedly decreased or even disappeared beyond week 16, except for one mouse that showed an increased bioluminescence signal at the jaw bone and hind limbs at week 22. These tumors were shown by IHC to contain Tg but lost AR and luciferase beyond week 16 in poorly differentiated prostate tumors.


CONCLUSIONS
A direct correlation between bioluminescence emission and AR expression was found in TRAMP-Luc tumor progression model. This model allows non-invasive imaging of prostate cancer metastases to bone and soft tissues.
Hsieh
Chia-Ling
CL
Molecular Urology and Therapeutic Program, Department of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. chsieh2@emory.edu
Xie
Zhihui
Z
Yu
Jie
J
Martin
W David
WD
Datta
Milton W
MW
Wu
Guang-Jer
GJ
Chung
Leland W K
LW
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000556:secondary; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics / Q000378:metabolism*
D000957:Antigens, Viral, Tumor; D008164:Luminescent Proteins; D011944:Receptors, Androgen; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506034:Tnfrsf25 protein, mouse; D008156:Luciferases; D017430:Prostate-Specific Antigen