Gleeson N, Gonsalves R, Bonnar J
Trinity College Department of Obstetrics & Gynaecology, St. Jame's Hospital, Dublin, Ireland.
Eur J Gynaecol Oncol. 1993;14(5):369-73.
Urokinase (u-PA) induced proteolysis of the extracellular matrix appears to be involved in stromal invasion by tumor cells and metastasis. Many malignant cells are known to secrete u-PA. Plasminogen activator inhibitor-type 2 (PAI-2) is an inhibitor of u-PA and is present in several neoplastic cell lines and malignant ascites. We measured u-PA and PAI-2 antigen in tissue homogenates of normal and malignant endometrium from 21 postmenopausal patients. Enzyme linked immunoassays which measure the bound and unbound, single and two chain form of the activators and bound and unbound form of the inhibitor were used. Urokinase was present in four of seven normal (range 0.15-0.5, median 0.15 ng/mg protein) and in all malignant endometrial homogenates (range 0.41-9.2, median 3.4 ng/mg protein), p < 0.001. PAI-2 was detectable in four of seven normal endometrial homogenates at low concentrations (range 1.1-3.1, median 1.1 ng/mg protein) and in all malignant tissue homogenates at higher levels (range 1.6-27.3, median 4.9 ng/mg protein), p < 0.01. Levels of PAI-2 were higher in Stage II/III compared to Stage I malignancy (p < 0.01) and in cancers that had invaded 50% or more of the uterine wall compared to less invasive cancers, p < 0.01. PAI-2 may be useful as a prognostic marker in endometrial cancer.
尿激酶(u-PA)诱导的细胞外基质蛋白水解似乎参与肿瘤细胞的基质侵袭和转移。已知许多恶性细胞会分泌u-PA。纤溶酶原激活物抑制剂2型(PAI-2)是u-PA的抑制剂,存在于多种肿瘤细胞系和恶性腹水中。我们检测了21名绝经后患者正常和恶性子宫内膜组织匀浆中的u-PA和PAI-2抗原。采用酶联免疫分析法,该方法可检测激活剂的结合态和游离态、单链和双链形式以及抑制剂的结合态和游离态。尿激酶存在于7例正常组织中的4例(范围0.15 - 0.5,中位数0.15 ng/mg蛋白),且存在于所有恶性子宫内膜匀浆中(范围0.41 - 9.2,中位数3.4 ng/mg蛋白),p < 0.001。在7例正常子宫内膜匀浆中的4例可检测到低浓度的PAI-2(范围1.1 - 3.1,中位数1.1 ng/mg蛋白),且在所有恶性组织匀浆中PAI-2水平更高(范围1.6 - 27.3,中位数4.9 ng/mg蛋白),p < 0.01。与I期恶性肿瘤相比,II/III期PAI-2水平更高(p < 0.01);与侵袭性较低的癌症相比,侵袭子宫壁50%或更多的癌症中PAI-2水平更高,p < 0.01。PAI-2可能作为子宫内膜癌的一种预后标志物。