Plasminogen activator inhibitor type 1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin via alpha(v)beta(5) integrin.
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.
Takahashi
Tsuyoshi
T
First Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka.
Suzuki
Kazuya
K
Ihara
Hayato
H
Mogami
Hideo
H
Kazui
Teruhisa
T
Urano
Tetsumei
T
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D024141:Collagen Type IV / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005354:Fibrosarcoma / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology; D019096:Vitronectin / Q000378:metabolism*
D024141:Collagen Type IV; D005353:Fibronectins; D016023:Integrins; D017395:Plasminogen Activator Inhibitor 1; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; D014568:Urokinase-Type Plasminogen Activator