Mars W M, Zarnegar R, Michalopoulos G K
Department of Pathology, University of Pittsburgh, Pennsylvania 15261.
Am J Pathol. 1993 Sep;143(3):949-58.
Hepatocyte growth factor, also known as scatter factor, is a complete mitogen for hepatocytes that bears sequence and structural homology with plasminogen. Because it exists in both a mitogenically inactive single-chain form and an active two-chain form, we were interested in determining whether plasminogen activators could properly cleave single-chain hepatocyte growth factor to generate active two-chain hepatocyte growth factor. Herein we report that both urokinase-type plasminogen activator and tissue-type plasminogen activator can cleave single-chain hepatocyte growth factor, generating two-chain hepatocyte growth factor. When equal quantities of plasminogen activator-treated and activator-untreated hepatocyte growth factor are compared in serum-free in vitro bioassays, the treated hepatocyte growth factor is mitotically more active. Also, urokinase-type plasminogen activator was inactive against hepatocyte growth factor molecules with a mutated cleavage site. This suggests that urokinase-type and tissue-type plasminogen activator may be natural biological regulators of hepatocyte growth factor. Because the active form of hepatocyte growth factor is a powerful stimulator of DNA synthesis and cell motility, these findings may be relevant in understanding the role of plasminogen activators in the biology of cancer invasion and metastasis.
肝细胞生长因子，也称为分散因子，是一种对肝细胞具有完全促有丝分裂作用的因子，它与纤溶酶原在序列和结构上具有同源性。由于它以有丝分裂无活性的单链形式和活性双链形式存在，我们有兴趣确定纤溶酶原激活剂是否能正确切割单链肝细胞生长因子以产生活性双链肝细胞生长因子。在此我们报告，尿激酶型纤溶酶原激活剂和组织型纤溶酶原激活剂都能切割单链肝细胞生长因子，产生双链肝细胞生长因子。在无血清体外生物测定中比较等量的经纤溶酶原激活剂处理和未处理的肝细胞生长因子时，经处理的肝细胞生长因子在有丝分裂方面更具活性。此外，尿激酶型纤溶酶原激活剂对具有突变切割位点的肝细胞生长因子分子无活性。这表明尿激酶型和组织型纤溶酶原激活剂可能是肝细胞生长因子的天然生物调节剂。由于肝细胞生长因子的活性形式是DNA合成和细胞运动的强大刺激剂，这些发现可能与理解纤溶酶原激活剂在癌症侵袭和转移生物学中的作用有关。
