Plasminogen Activator Inhibitor Type 1 Promotes Fibrosarcoma Cell Migration by Modifying Cellular Attachment to Vitronectin via α_vβ₅ Integrin

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 α_vβ₅ 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-α_vβ₅ 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 α_vβ₅ integrin. This may be related to their tumor-promoting effect.

KEYWORDS

PAI-1 - u-PA - α_vβ₅ integrin - cell migration

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