The urokinase/urokinase-receptor system and cancer invasion

u-PA binds with high affinity to its specific GPI-anchored receptor on the cell surface. The binding has at least two important consequences: (1) it enhances the rate of plasminogen activation on the cell surface; and (2) it focuses the u-PA proteolytic activity at the leading front of migrating cells. Several recent findings suggest that surface-bound u-PA is essential for the invasive ability of tumour cells, even if a picture is emerging indicating a concerted action with other proteases, like collagenases and cathepsin B (Kobayashi et al, 1992; Ossowski, 1992; Schmitt et al, 1992; (Danø et al, 1994). In some tumours, e.g. colon, breast and skin cancer, in situ hybridization studies have given an insight into the u-PA/u-PAR tumour biology showing a complex interplay between stromal and cancer cells Danø et al, 1994). u-PA, u-PAR, and PAI-1 tumour content are now well established prognostic factor in breast cancer. This body of knowledge could be used for theurapeutic purposes. For example, a large study with 671 patients has allowed the identification of node-negative patients which, according to their u-PA levels, would need adjuvant therapy (Foekens et al, 1992). Many other tumours, especially colorectal cancer, expect a direct clinical evaluation of u-PA, u-PAR and serpins as prognostic factors.