Expression of proteinase-activated receptor-2 in human pancreatic cancer: a possible relation to cancer invasion and induction of fibrosis.
The proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin. To clarify the presence of PAR-2 in human pancreatic cancer, the expression of PAR-2 was analyzed by RT-PCR, immunoblotting and immunocytochemistry using 5 human pancreatic cancer cell lines. And to evaluate the biological significance, immunohistochemical expression of PAR-2 in malignant and non-malignant human pancreatic tissues was examined using paraffin-embedded sections. The presence of PAR-2 was confirmed in all 5 pancreatic cancer cell lines and all 21 paraffin-embedded specimens from human pancreatic cancer examined. The expression of PAR-2 was found to be higher in the tissues with infiltrative growth pattern than those with expansive growth pattern. Moreover, significantly higher expression of PAR-2 was observed in the tissues which were accompanied by severe fibrosis. Even in the same specimen, the intensity of immunoreactivity tended to be stronger in the part with severe fibrosis than that with mild fibrosis. Similarly, the higher expression of PAR-2 was observed in chronic pancreatitis with severe fibrosis than with mild fibrosis. Taken together, these results suggest that the activation of PAR-2 is involved in cancer invasion and the induction of fibrosis in human pancreatic cancer.
Ikeda
Osamu
O
Department of Surgery II, Kumamoto University Medical School, Kumamoto, Japan.
Egami
Hiroshi
H
Ishiko
Takatoshi
T
Ishikawa
Shinji
S
Kamohara
Hidenobu
H
Hidaka
Hideki
H
Mita
Seiji
S
Ogawa
Michio
M
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D005355:Fibrosis; D006801:Humans; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin