목 적 : 악성 종양에 있어서 단백질 분해 효소에 의한 세포외기질의 분해는 종양 침습 및 전이에 있어서 중요한 역할을 한다. Urokinase-type plasminogen activator(u-PA)는 이러한 단백질 분해효소 중 하나이며, u-PA의 길항제인 plasminogen activator inhibitor(PAI-1, PAI-2)도 u-PA에 의한 종양조직 자체의 분해를 방어하여 종양의 성장, 침습 및 혈관신생을 촉진하는 역할을 한다. u-PA와 PAI-1은 폐암 등의 종양 조직내의 양이 증가하며, 침습도 및 예후 둥과 유의하게 상관되는 것으로 보고되고 있다. 저자 등은 폐암환자의 혈장 u-PA와 PAI-1의 농도를 측정하여 조직형 및 병기와의 관련성을 조사해 보고자 한다. 방 법 : 폐암 환자 37예, 여러 가지 양성 폐질환 환자 21예 및 유사연령의 정상 대조군 24예에서 혈장 u-PA 및 PAI-1 항원의 농도를 ELISA법으로 측정하였다. 결 과 : 혈장 u-PA 항원 농도는 정상 대조군에서 $1.0{pm}0.3ng/mL$, 양성 폐질환군에서 $1.0{pm}0.3ng/mL$, 폐암환자군에서 $0.9{pm}0.3ng/mL$로 유의한 차이가 없었다. 혈장 PAI-1 항원 농도는 정상 대조군에서 $14.2{pm}6.7ng/mL$, 양성 폐질환군에서 $14.9{pm}6.3ng/mL$, 폐암 환자군에서 $22.1{pm}9.8ng/mL$로 폐암 환자에서 정상 대조군 및 양성 폐질환군에 비하여 유의하게 높았다. 혈장 u-PA 항원 농도는 편평상피암에서 $0.7{pm}0.4ng/mL$, 선암에서 $0.8{pm}0.3ng/mL$, 대세포암에서 0.9ng/mL, 소세포암에서 $1.1{pm}0.7ng/mL$로 유의한 차이가 없었다. 혈장 PAI-1 항원 농도는 편평상피암에서 $22.3{pm}7.2ng/mL$, 선암에서 $22.6{pm}9.9ng/mL$, 대세포암에서 42ng/mL, 소세포암에서 $16.0{pm}14.2ng/mL$로 유의한 차이가 없었다. u-PA 항원 농도는 stage I에서 0.74ng/mL, stage II에서 $1.2{pm}0.6ng/mL$, stage IIIA에서 $0.7{pm}0.4ng/mL$, stage IIIB에서 $0.7{pm}0.4ng/mL$, stage IV에서 $0.7{pm}0.3ng/mL$였고, 혈장 PAI-1 항원 농도는 stage I에서 21.8ng/mL, stage II에서 $22.7{pm}8.7ng/mL$, stage IIIA에서 $18.4{pm}4.9ng/mL$, stage IIIB에서 $25.3{pm}9.0ng/mL$, stage IV에서 $21.5{pm}10.8ng/mL$로 유의한 차이가 없었다. 폐암 환자에서 T기를 T1-3 와 T4로 나누어서 비교를 한 결과, 혈장 u-PA 항원 농도는 T1-3에서 $0.8{pm}0.4ng/mL$였고 T4에서 $0.7{pm}0.4ng/mL$로 차이가 없었으나, 혈장 PAI-1 항원 농도는 T1-3에서 $17.9{pm}5.6ng/mL$였고 T4에서 $26.1{pm}9.1ng/mL$로 T4에서 유의하게 높았다. 혈장 u-PA 항원 농도는 M0에서 $0.8{pm}0.4ng/mL$, M1에서 $0.7{pm}0.3ng/mL$였고, 혈장 PAI-1 항원 농도는 M0에서 $23.6{pm}8.3ng/mL$, M1에서 $21.5{pm}10.8ng/mL$로 유의한 차이가 없었다. 결 론 : 이상의 결과에서 폐암 환자에서 혈장 PAI-1은 정상대조군 및 양성 폐질환에 비하여 특이적으로 증가하였고, 또한 폐암의 국소적 침습 정도와의 관련성을 보여 주었다.
Background : Cancer invasion and metastasis require the dissolution of the extracellular matrix in which several proteolytic enzymes are involved. One of these enzymes is the urokinase-type plasminogen activator(u-PA), and plasminogen activator inhibitors(PAI-1, PAI-2) also have a possible role in cancer invasion and metastasis by protection of cancer itself from proteolysis by u-PA. It has been reported that the levels of u-PA and plasminogen activator inhibitors in various cancer tissues are significantly higher than those in normal tissues and have significant correlations with tumor size and lymph node involvement. Here, we measured the concentration of plasma u-PA and PAI-1 antigens in the patients with lung cancer and compared the concentration of them with histologic types and staging parameters. Methods : We measured the concentration of plasma u-PA and PAI-1 antigens using commercial ELISA kit in 37 lung cancer patients, 21 benign lung disease patients and 24 age-matched healthy controls, and we compared the concentration of them with histologic types and staging parameters in lung cancer patients. Results : The concentration of u-PA was $1.0{pm}0.3ng/mL$ in controls, $1.0{pm}0.3ng/mL$ in benign lung disease patients and $0.9{pm}0.3ng/mL$ in lung cancer patients. The concentration of PAI-1 was $14.2{pm}6.7ng/mL$ in controls, $14.9{pm}6.3ng/mL$ in benign lung disease patients, and $22.1{pm}9.8ng/mL$ in lung cancer patients. The concentration of PAI-1 in lung cancer patients was higher than those of benign lung disease patients and controls. The concentration of u-PA was $0.7{pm}0.4ng/mL$ in squamous cell carcinoma, $0.8{pm}0.3ng/mL$ in adenocarcinoma, 0.9ng/mL in large cell carcinoma, and $1.1{pm}0.7ng/mL$ in small cell carcinoma. The concentration of PAI-1 was $22.3{pm}7.2ng/mL$ in squamous cell carcinoma, $22.6{pm}9.9ng/mL$ in adenocarcinoma, 42 ng/mL in large cell carcinoma, and $16.0{pm}14.2ng/mL$ in small cell carcinoma. The concentration of u-PA was 0.74ng/mL in stage I, $1.2{pm}0.6ng/mL$ in stage II, $0.7{pm}0.4ng/mL$ in stage IIIA, $0.7{pm}0.4ng/mL$ in stage IIIB, and $0.7{pm}0.3ng/mL$ in stage IV. The concentration of PAI-1 was 21.8ng/mL in stage I, $22.7{pm}8.7ng/mL$ in stage II, $18.4{pm}4.9ng/mL$ in stage IIIA, $25.3{pm}9.0ng/mL$ in stage IIIB, and $21.5{pm}10.8ng/mL$ in stage IV. When we divided T stage into T1-3 and T4, the concentration of u-PA was $0.8{pm}0.4ng/mL$ in T1-3 and $0.7{pm}0.4ng/mL$ in T4, and the concentration of PAI-1 was $17.9{pm}5.6ng/mL$ in T1-3 and $26.1{pm}9.1ng/mL$ in T4. The concentration of PAI-1 in T4 was significantly higher than that in T1-3. The concentration of u-PA was $0.8{pm}0.4ng/mL$ in M0 and $0.7{pm}0.3ng/mL$ in M1, and the concentration of PAI-1 was $23.6{pm}8.3ng/mL$ in M0 and $21.5{pm}10.8ng/mL$ in M1. Conclusions : The plasma levels of PAI-1 in lung cancer were higher than benign lung disease and controls, and the plasma levels of PAI-1 in T4 were significantly higher than T1-3. These findings suggest involvement of PAI-1 with local invasion of lung cancer, but it should be confirmed by the data on comparison with pathological staging and tissue level in lung cancer.
