<原著>胃癌および大腸・直腸癌の癌組織中におけるplasminogen activator inhibitor 1
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An increase of urokinase-type plasminogen activator (u-PA) has been suggested to be an indicator of carcinogenesis as well as of transformation of cells. In the present study, plasminogen activator inhibitor 1 (PAI-1) was measured in the tissue of the stomach and colorectal carcinoma, as compared to the levels in normal stomach and colorectal mucosa. The stomach and colorectal carcinoma tissue plus normal mucosa were divided macroscopically into three portions : the central part of the carcinoma, the marginal part of the carcinoma, and normal mucosa. Among these, the highest levels of PAI-1 antigen were found in the central part of the carcinoma. Sandwich enzyme immunoassay revealed that the total PAI-1 antigen in the central part of the stomach and colorectal carcinoma were 1.54±1.37 and 1.46±1.18 ng/mg, respectively, while no PAI-1 antigen or activity was observed in the normal mucosa. The PAI-1 showed a non-lytic zone with a molecular weight of 54 kDa by reverse fibrin autography, and this 54 kDa band reacted with anti-PAI-1 lgG on an immunoblotted nitrocellulose membrane by the ABC method. Electrophoretic enzymography demonstrated that all three portions showed four lytic bands with molecular weights of 33,55,72 and 80 kDa. The 33 and 55 kDa bands were identified as u-PA, and the 72 kDa band was identified as tissue-type PA (t-PA). The transformed tissue such as the central and marginal parts of the carcinoma revealed an extra band of 100 kDa which reacted with anti-u-PA lgG. Although the total PA activity was unchanged in colorectal carcinoma, the ratio of the u-PA content to total PA was increased 2.6-fold and 2-fold in the central part of stomach and colorectal carcinoma, respectively, as compared to that in the normal mucosa. It is suggested that the increased PA activity, due mainly to u-PA, contributes to the proteolytic action of the tumor cells for invasion or metastasis but the function of u-PA is regulated by the PAI in the tumor tissue. We conclude that increased level of PAI-1 and u-PA may serve as possible markers of carcinogenesis.
- 近畿大学の論文
- 1990-06-25
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