Influences of the lysosomal associated membrane proteins (Lamp-1, Lamp-2) and Mac-2 binding protein (Mac-2-BP) on the prognosis of pancreatic carcinoma.
BACKGROUND
Lamps and Mac-2-BP are ligands of galectin-3, and they were suggested to influence tumor proliferation and metastasis formation. The authors studied the expression of Lamp-1, Lamp-2, and Mac-2-BP in pancreatic carcinoma and evaluated their influence on patient prognosis.


METHODS
Northern blot analysis, in situ hybridization, and immunohistochemistry were performed in 12 normal and 28 pancreatic carcinoma tissue samples and in pancreatic carcinoma cell lines. The molecular findings in the tumor samples were correlated with the prognosis and histopathologic tumor characteristics. In addition, in Lamp-1 transfected CAPAN-1 pancreatic carcinoma cells, cell proliferation was analyzed.


RESULTS
Lamp-1, Lamp-2, and Mac-2-BP were overexpressed in 61% (1.6-fold increase, not significant), 71% (3.0-fold increase, P < 0.01), and 93% (5.6-fold increase, P < 0.01) of the pancreatic carcinoma samples. Lamp-1 and Lamp-2 immunoreactivity was present at the luminal side of the ductal carcinoma cells whereas Mac-2-BP immunoreactivity was diffusely spread over the whole cytoplasm and the nucleolus of ductal carcinoma cells. Correlation of the molecular data with clinical patient parameters revealed that patients whose tumors exhibited high Lamp-1 mRNA expression lived significantly longer (median, 17 months) after tumor resection than patients whose tumors exhibited low to moderate Lamp-1 mRNA levels (median, 8 months; P < 0.02). No relation between Lamp-2 and Mac-2-BP mRNA expression and any of the histopathologic parameters was found. Lamp-1 transfected CAPAN-1 cells showed decreased cell growth compared with the nontransfected cells.


CONCLUSIONS
Lamp-1 might influence local tumor progression rather than the formation of tumor metastasis in pancreatic carcinoma, whereas Mac-2-BP and Lamp-2 seem to have little influence on these parameters in pancreatic carcinoma.
Künzli
Beat M
BM
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Bern, Switzerland.
Berberat
Pascal O
PO
Zhu
Zhaowhen W
ZW
Martignoni
Marcus
M
Kleeff
Jörg
J
Tempia-Caliera
Adrien A
AA
Fukuda
Minoru
M
Zimmermann
Arthur
A
Friess
Helmut
H
Büchler
Markus W
MW
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015152:Blotting, Northern; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D002461:Cell Line, Transformed; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051907:Lysosomal Membrane Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D016326:Extracellular Matrix Proteins
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins