Increased expression of MUC18 correlates with the metastatic progression of mouse prostate adenocarcinoma in the TRAMP model.
OBJECTIVE
The transgenic adenocarcinoma mouse prostate (TRAMP) model is a paradigm that closely mimics the progression of clinical prostate cancer. We have previously reported that MUC18, a cell adhesion molecule in the Ig gene superfamily, is a marker as well as an important mediator for the metastatic potential of human prostate cancer cells. In this study we investigated the possible correlation of increased MUC18 expression with the malignant progression of prostate cancer in the TRAMP model.


METHODS
We used immunohistochemistry, Western blot and reverse transcriptase-polymerase chain reaction analyses to determine MUC18 expression in the prostate gland of 178 to 282-day-old TRAMP positive males with a prostate tumor size of 0.4 to 12.7 gm. Eight normal prostates, 10 prostates with high grade prostatic intraepithelial neoplasia (PIN), 24 prostates with primary prostate cancer, 10 metastatic lesions from 50 pure C57BL/6 TRAMP mice (Wu colony) and 2 normal prostates, 2 prostates with high grade PIN, 6 prostates with primary prostate cancer and 4 metastatic lesions from 10 [C57BL/6 TRAMP x FVB] F1 mice (NMG colony) were used.


RESULTS
We found that mouse MUC18 was expressed in all (100%) high grade PIN, adenocarcinomas and metastatic lesions. All mice bearing primary prostate tumors had prostate cancer metastatic to the peri-aortic lymph nodes and some had it to other organs (liver, lung, kidney, testes, seminal vesicles and abdominal cavity). In contrast, prostates from 10 nontransgenic littermates did not have detectable MUC18 expression.


CONCLUSIONS
MUC18 expression is up-regulated in the TRAMP model and it correlates with the malignant progression of mouse prostate adenocarcinoma in this transgenic model. This further strengthens the hypothesis that MUC18 has an important role in increasing the metastatic potential of prostate cancer cells.
Wu
Guang-Jer
GJ
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. wu@microbio.emory.edu
Fu
Pingping
P
Chiang
Cheng-Feng
CF
Huss
Wendy J
WJ
Greenberg
Norman M
NM
Wu
Mei-Whey H
MW
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D051929:CD146 Antigen; D018450:Disease Progression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051929:CD146 Antigen; C497903:Mcam protein, mouse; D019006:Neural Cell Adhesion Molecules