Expression of cancer testis antigens in pancreatic carcinoma cell lines, pancreatic adenocarcinoma and chronic pancreatitis.
In order to define antigens that might be suitable as vaccines for pancreatic carcinoma, we investigated the composite expression of 10 cancer testis (CT) antigens (SCP-1, NY-ESO-1, SSX-1, SSX-2, SSX-4, GAGE, MAGE-3, MAGE-4, CT-7 and CT-8) by Reverse Transcriptase-PCR (RT-PCR) in fresh biopsies of human pancreatic adenocarcinoma, chronic pancreatitis and pancreatic carcinoma cell lines. While all CT genes were frequently expressed in cell lines derived from pancreatic cancer, no expression of MAGE-3, SSX-1, SSX-2, NY-ESO-1 and CT-7 was detected in fresh tumor biopsies, and MAGE-4 (1/52), SSX-4 (1/39) and CT-8 (2/41) were only rarely expressed. In contrast, HOM-TES-14/SCP-1 was expressed in 48% (29/61) and GAGE in 21% (13/61) of cases, respectively. One CT gene was expressed by 59% (75% in male, 46% in female patients; p = 0.05) and 2 or more CT genes by 15% of the samples. SCP-1 protein expression correlated well with mRNA expression. While SCP-1 and GAGE were absent in normal pancreas, they were found in 2/8 (SCP-1) and 1/8 (GAGE) samples of chronic pancreatitis, respectively, supporting the concept of chronic pancreatitis as a premalignant condition. SCP-1 and GAGE represent promising candidates for vaccine development in pancreatic carcinoma. Whether SCP-1 and GAGE expression identify cases of chronic pancreatitis with a high risk of malignant transformation remains to be shown.
Kubuschok
Boris
B
Department of Internal Medicine I, University of Saarland Medical School, Homburg/Saar, Germany.
Xie
Xiaoxiun
X
Jesnowski
Ralf
R
Preuss
Klaus-Dieter
KD
Romeike
Bernd F M
BF
Neumann
Frank
F
Regitz
Evi
E
Pistorius
Georg
G
Schilling
Martin
M
Scheunemann
Peter
P
Izbicki
Jakob R
JR
Löhr
J-Matthias
JM
Pfreundschuh
Michael
M
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D010195:Pancreatitis / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012439:Saccharin / Q000031:analogs & derivatives* / Q000378:metabolism; D013737:Testis / Q000378:metabolism*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D004268:DNA-Binding Proteins; C113434:GAGE7 protein, human; C456621:LUZP4 protein, human; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins; C118048:SCP 1; C093962:synovial sarcoma X breakpoint proteins; D000082:Acetaminophen; D012439:Saccharin