Delbaldo C, Masouye I, Saurat J H, Vassalli J D, Sappino A P
Division of Onco-Haematology, University of Geneva Medical School, Switzerland.
Cancer Res. 1994 Aug 15;54(16):4547-52.
A large body of experimental evidence suggests that plasminogen activators provide tumoral cells with efficient means to degrade extracellular matrix constituents and thereby facilitate their dissemination to distant sites. Melanocytic neoplasia encompass a spectrum of lesions exhibiting diverse clinical behavior that remain difficult to predict with current histopathological evaluations. Little information concerning the contribution of plasminogen activation in diagnostic specimens of human melanocytic tumors is presently available. We thus analyzed biopsy specimens of pigmented skin lesions by histological techniques that identify the cellular sites of synthesis of plasminogen activators and of their inhibitors and that localize the sites of plasminogen activators-catalyzed enzymatic activities. We found that urokinase-type plasminogen activators (uPA) and plasminogen activator inhibitor type 1 mRNAs accumulate in atypical nevocytes and in melanoma cells, but not in benign nevocytes. However, uPA-catalyzed proteolytic activity was detected exclusively in melanomas. These observations suggest that up-regulation of the uPA gene is an early feature of melanocyte transformation and that unbalanced enzyme/inhibitor activity is associated with the malignant phenotype. By supporting a role for uPA in melanoma invasiveness, they provide a novel tool for the evaluation of atypia in nevi.
大量实验证据表明，纤溶酶原激活剂为肿瘤细胞提供了有效手段来降解细胞外基质成分，从而促进其扩散至远处部位。黑素细胞肿瘤包括一系列表现出不同临床行为的病变，目前通过组织病理学评估仍难以预测。目前关于纤溶酶原激活在人类黑素细胞肿瘤诊断标本中的作用的信息很少。因此，我们通过组织学技术分析色素性皮肤病变的活检标本，这些技术可识别纤溶酶原激活剂及其抑制剂的合成细胞位点，并定位纤溶酶原激活剂催化的酶活性位点。我们发现，尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂1 mRNA在非典型痣细胞和黑色素瘤细胞中积累，但在良性痣细胞中不积累。然而，仅在黑色素瘤中检测到uPA催化的蛋白水解活性。这些观察结果表明，uPA基因的上调是黑素细胞转化的早期特征，并且酶/抑制剂活性失衡与恶性表型相关。通过支持uPA在黑色素瘤侵袭中的作用，它们为评估痣的异型性提供了一种新工具。
