Localization of urokinase-type plasminogen activator, plasminogen activator inhibitor-1, 2 and plasminogen in colon cancer.
We examined the localization of urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitors (PAI-1 and PAI-2) and plasminogen (plg) in 26 cases of colon cancer by immunohistochemical staining. The u-PA antigen was detected in the cytoplasm of cancer cells (18/26) and stromal cells adjacent to cancer tissues (9/26). The localization of u-PA mRNA examined by in situ hybridization was consistent with that of u-PA antigen. The PAI-1 antigen was detected in fibroblasts and endothelial cells (22/26), while PAI-2 antigen was found in cancer cells (20/26). The plg antigen was seen in the extracellular matrix of the cancer stroma. The u-PA expression in cancer cells was significantly more frequently detected in cases with lymph node metastasis than in cases without metastasis. In either PAI-1- or PAI-2-expressing cases, lymph node metastasis seemed to be restrained. These findings indicate that cancer cells themselves produce u-PA, and suggest that u-PA converts plg into plasmin, which dissolves the extracellular matrix surrounding cancer cells, resulting in cancer invasion and metastasis. PAI-1 and PAI-2 may have inhibitory actions on cancer invasion and metastasis mediated by u-PA.
Naitoh
H
H
First Department of Surgery, Shiga University of Medical Science.
Eguchi
Y
Y
Ueyama
H
H
Kodama
M
M
Hattori
T
T
D003110:Colonic Neoplasms / Q000737:chemistry* / Q000648:ultrastructure; D003593:Cytoplasm / Q000737:chemistry; D004727:Endothelium / Q000737:chemistry; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D010958:Plasminogen / Q000032:analysis*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000737:chemistry; D014018:Tissue Distribution; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis* / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator