A role for protease-activated receptor-2 in pancreatic cancer cell proliferation.
The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin and tryptase. The purpose of this study was to clarify the role of PAR-2 in proliferation of human pancreatic cancer cells. PAR-2 mRNA and protein expression were detected by RT-PCR and Western blotting in three cell lines, SW1990, Capan-2, and Panc-1. The PAR-2 agonist peptide, SLIGKV (25, 50 micro g/ml) and trypsin (10, 100 ng/ml) significantly increased cell proliferation. Enhancement of MAP kinase also was observed in cancer cells treated with SLIGKV and trypsin. In vivo, subcutaneous xenografted tumors showed significantly enhanced growth after treatment with SLIGKV. Tumor-associated trypsinogen (TAT) mRNA and protein expression was detected in SW1990 and Capan-2, suggesting autocrine trypsin production. PAR-2 activated by trypsin plays an important role in promoting proliferation of pancreatic cancer.
Shimamoto
Rie
R
Department of Surgical Oncology (First Department of Surgery), Osaka City University Graduate School of Medicine, Osaka, Japan.
Sawada
Tetsuji
T
Uchima
Yasutake
Y
Inoue
Masafumi
M
Kimura
Kenjiro
K
Yamashita
Yoshito
Y
Yamada
Nobuya
N
Nishihara
Tamahiro
T
Ohira
Masaichi
M
Hirakawa
Kosei
K
D000818:Animals; D019898:Autocrine Communication; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009842:Oligopeptides / Q000633:toxicity*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014357:Trypsin / Q000494:pharmacology; D014362:Trypsinogen / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; D012333:RNA, Messenger; D044464:Receptor, PAR-2; C109968:seryl-leucyl-isoleucyl--glycyl-lysyl-valine; D014362:Trypsinogen; D020928:Mitogen-Activated Protein Kinases; D014357:Trypsin