Choi Yang-Kyu, Yoon Byung-Il, Kook Yoon-Hoh, Won Young-Suk, Kim Jin-Hyun, Lee Chul-Ho, Hyun Byung-Hwa, Oh Goo-Taeg, Sipley John, Kim Dae-Yong
Korea Research Institute of Bioscience and Biotechnology, Taejon, 305-333, Korea.
Jpn J Cancer Res. 2002 Feb;93(2):151-6. doi: 10.1111/j.1349-7006.2002.tb01253.x.
The significance of urokinase-type plasminogen activator (uPA) expression in gastric cancer development was tested by using a human uPA cDNA transfection approach and an in vivo severe combined immunodeficient (SCID) mouse model. The AGS gastric cancer cell line, which has urokinase-type plasminogen-activator receptor (uPAR) but lacks uPA, was transfected with a plasmid containing human uPA cDNA and injected into the backs of SCID mice. Compared with the parent AGS cells, uPA protein secretion in AGS-2-, AGS-4-, and AGS-8-transfected cells increased by 26.1-, 34.6-, and 4.8-fold, respectively (P < 0.05). mRNA expression levels of uPA in the AGS-4 clone were much stronger than those in AGS-2 and AGS-8 clones. After the cancer cells (2 x 10(6)) were injected s.c. into the SCID mice, a palpable mass was observed at the injection site at around 140 days post-injection, followed by accelerated growth of the xenograft up to 180 days post-injection only in the high uPA-producing clone (AGS-4). These results suggest that continuous and high production of uPA by tumor cells is one of the important factors reflecting the malignancy of gastric cancer cells.
通过使用人尿激酶型纤溶酶原激活剂（uPA）cDNA转染方法和体内严重联合免疫缺陷（SCID）小鼠模型，测试了uPA表达在胃癌发展中的意义。将含有尿激酶型纤溶酶原激活剂受体（uPAR）但缺乏uPA的AGS胃癌细胞系用含有人uPA cDNA的质粒转染，并注射到SCID小鼠的背部。与亲本AGS细胞相比，AGS-2、AGS-4和AGS-8转染细胞中的uPA蛋白分泌分别增加了26.1倍、34.6倍和4.8倍（P < 0.05）。AGS-4克隆中uPA的mRNA表达水平比AGS-2和AGS-8克隆中的要强得多。将癌细胞（2×10⁶）皮下注射到SCID小鼠体内后，在注射后约140天时在注射部位观察到可触及的肿块，随后仅在高uPA产生克隆（AGS-4）中，异种移植在注射后180天内加速生长。这些结果表明，肿瘤细胞持续高产量产生uPA是反映胃癌细胞恶性程度的重要因素之一。
