The expression of a type II transmembrane serine protease (Seprase) in human gastric carcinoma.
OBJECTIVE
The invasion and metastasis of carcinoma cells require the proteolytic degradation of the extracellular matrix by various cell surface proteases. Among these, seprase is a type II transmembrane serine protease absent in normal tissues and it has been implicated in the invasion of the extracellular matrix by both tumor and stromal cells in human breast carcinoma and melanoma. In the present study, the expression of seprase mRNA, protein and its gelatin-degrading activity in human gastric carcinoma were examined to substantiate the potential role of seprase in gastric carcinoma invasion.


METHODS
We have examined the seprase expression in human gastric carcinoma (n = 34) by RT-PCR, Western immunoblotting analysis, immunohistochemistry, and gelatin zymography.


RESULTS
Immunoblotting analysis using mAb D8 directed against seprase showed that the carcinoma tissues in 26 out of 34 cases of gastric cancer expressed a dimeric form of seprase but their normal counterparts did not. Gelatin zymography confirmed that the isolated seprase exhibited the gelatin-degrading activity and was active. Seprase-expressing carcinoma tissues were more often found in the scirrhous type than in other types of gastric carcinoma. RT-PCR analysis showed that seprase mRNA was present in carcinoma tissues but not in normal tissues. Immunohistochemically, seprase was mainly located in gastric carcinoma cells, weakly in stromal cells and microvessel endothelial cells in the tumor nest, and none in normal cells.


CONCLUSIONS
Our studies showed the unique expression and localization of seprase in the tumor and stromal cells within human gastric carcinoma but not in normal tissues, suggesting a role of seprase in the invasive and metastatic progression of gastric carcinoma.
Mori
Yoshiyuki
Y
Department of Pathology, School of Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. yoshim@ka3.so-net.ne.jp
Kono
Koji
K
Matsumoto
Yoshirou
Y
Fujii
Hideki
H
Yamane
Tetsu
T
Mitsumata
Masako
M
Chen
Wen-Tien
WT
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D010450:Endopeptidases; D018093:Gelatinases / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D000099167:Fibroblast Activation Protein Alpha
D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha