Urokinase type plasminogen activator and its receptor regulate the invasive potential of gastric cancer cell lines.
To assess the role of urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) on the invasive potential of cancer cells, in vitro experiments were performed using two human gastric cancer cell lines, NUGC-3 and MKN-28. NUGC-3 cells secreted a higher level of uPA than MKN-28 cells, while the uPAR expression of NUGC-3 cells was lower than that of MKN-28 cells. Both cancer cell lines expressed Met protein and did not express hepatocyte growth factor (HGF). In Matrigel invasion assay, MKN-28 cells demonstrated significantly lower invasion index than NUGC-3 cells. The addition of exogenous uPA significantly increased the invasive activity of MKN-28 cells. The uPA expression in NUGC-3 cells was enhanced by adding conditioned media of fibroblast cells or HGF. These results suggest that uPA promotes the invasive capacity of the uPAR-positive cancer cells, and that stromal cells may play an important role in cancer cell invasion by supplying uPA and/or promoting uPA production.
Okusa
Y
Y
Department of Surgery I, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan. yokusa-boe@umin.ac.jp
Ichikura
T
T
Mochizuki
H
H
Shinomiya
N
N
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D002454:Cell Differentiation; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D017077:Culture Media, Conditioned; D009363:Neoplasm Proteins; C524898:PLAUR protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D017228:Hepatocyte Growth Factor; D014568:Urokinase-Type Plasminogen Activator