Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer.
In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinase-type plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P< 0.01) and lymph node metastasis (P< 0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P< 0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P< 0.01), lymph node metastasis and depth of invasion (P< 0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.
Kawasaki
K
K
First Department of Surgery, Kobe University School of Medicine, Japan.
Hayashi
Y
Y
Wang
Y
Y
Suzuki
S
S
Morita
Y
Y
Nakamura
T
T
Narita
K
K
Doe
W
W
Itoh
H
H
Kuroda
Y
Y
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator