1型纤溶酶原激活物抑制剂通过α(v)β(5)整合素改变细胞与玻连蛋白的附着，从而促进纤维肉瘤细胞迁移。

Plasminogen activator inhibitor type 1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin via alpha(v)beta(5) integrin.

作者信息

Takahashi Tsuyoshi, Suzuki Kazuya, Ihara Hayato, Mogami Hideo, Kazui Teruhisa, Urano Tetsumei

机构信息

First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka.

出版信息

Semin Thromb Hemost. 2005 Jun;31(3):356-63. doi: 10.1055/s-2005-872444.

DOI:10.1055/s-2005-872444

PMID:16052409

Abstract

Both urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1) are associated with a poor prognosis in cancer patients. We demonstrate that PAI-1 inhibits human fibrosarcoma cell (HT-1080) adhesion to vitronectin (Vn) via alpha (v)beta (5) integrin, and stimulates cell migration from Vn toward collagen type IV (Col). The cells attached more strongly to Vn and Col than to fibronectin (Fn), whereas PAI-1 interfered with cell attachment to Vn only. An integrin antagonist, RGD peptide, and anti-alpha (v)beta (5) integrin antibodies, which similarly inhibited cell attachment to Vn, also stimulated cell migration from Vn toward Col. u-PA did not modify cell attachment directly, but reversed the PAI-1-mediated inhibitory effect on cell adhesion to Vn, and its stimulatory effect on cell migration from Vn toward Col. Thus HT-1080 cell migration appears to be modified by u-PA and PAI-1, altering cell adhesion to Vn via alpha (v)beta (5) integrin. This may be related to their tumor-promoting effect.

摘要

尿激酶型纤溶酶原激活剂（u-PA）和纤溶酶原激活剂抑制剂1型（PAI-1）均与癌症患者的不良预后相关。我们证明，PAI-1通过α(v)β(5)整合素抑制人纤维肉瘤细胞（HT-1080）与玻连蛋白（Vn）的黏附，并刺激细胞从Vn向IV型胶原（Col）迁移。这些细胞与Vn和Col的黏附比与纤连蛋白（Fn）的黏附更强，而PAI-1仅干扰细胞与Vn的黏附。一种整合素拮抗剂RGD肽和抗α(v)β(5)整合素抗体同样抑制细胞与Vn的黏附，也刺激细胞从Vn向Col迁移。u-PA不会直接改变细胞黏附，但可逆转PAI-1介导的对细胞与Vn黏附的抑制作用及其对细胞从Vn向Col迁移的刺激作用。因此，HT-1080细胞的迁移似乎受到u-PA和PAI-1的影响，通过α(v)β(5)整合素改变细胞与Vn的黏附。这可能与其促肿瘤作用有关。