Inoue Masafumi, Sawada Tetsuji, Uchima Yasutake, Kimura Kenjiro, Nishihara Tamahiro, Tanaka Hiroaki, Yashiro Masakazu, Yamada Nobuya, Ohira Masaichi, Hirakawa Kosei
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Oncol Rep. 2005 Dec;14(6):1445-51.
Plasminogen activator inhibitor-1 (PAI-1) is a unique type of serine protease inhibitor and one of the key regulators of tumor invasion and metastasis. The purpose of this study was to elucidate the effect of PAI-1 gene transfection on liver metastasis and its mechanism by using the human high liver metastasis pancreatic cancer cell line, SW1990. PAI-1-transfected SW1990 (SW/PAI-1) produced a significantly higher level of PAI-1 in supernatant than parental cells. While no difference was observed for the production of u-PA and u-PA activity in the supernatant, cell proliferation of SW/PAI-1 was slightly suppressed on the 7th day of incubation compared to parental cells. Cellular invasion, in vivo tumorigenesis in xenograft and liver metastasis were significantly suppressed in SW/PAI-1 cells compared to parental cells. The angiogenesis of xenograft by detecting microvascular density and the production of metastasis-related factors, such as VEGF and TGF-beta1, were also decreased in SW/PAI-1 cells. These findings suggested that PAI-1 gene transfection might have the ability to prevent the liver metastasis of pancreatic cancer by modulating angiogenesis.
纤溶酶原激活物抑制剂-1（PAI-1）是一种独特的丝氨酸蛋白酶抑制剂，也是肿瘤侵袭和转移的关键调节因子之一。本研究的目的是通过使用人高肝转移潜能胰腺癌细胞系SW1990，阐明PAI-1基因转染对肝转移的影响及其机制。PAI-1转染的SW1990细胞（SW/PAI-1）培养上清中PAI-1的水平显著高于亲本细胞。虽然上清中尿激酶型纤溶酶原激活物（u-PA）的产生及其活性未观察到差异，但与亲本细胞相比，SW/PAI-1细胞在培养第7天时细胞增殖略有抑制。与亲本细胞相比，SW/PAI-1细胞的细胞侵袭、异种移植瘤体内成瘤及肝转移均受到显著抑制。通过检测微血管密度评估的异种移植瘤血管生成以及转移相关因子如血管内皮生长因子（VEGF）和转化生长因子-β1（TGF-β1）的产生在SW/PAI-1细胞中也有所降低。这些发现提示，PAI-1基因转染可能通过调节血管生成来预防胰腺癌的肝转移。
