Surface-associated plasminogen activation in leukemic cells: interaction with extracellular matrix

In WEHI-3B murine leukemic cells, plasminogen activator and plasminogen binding sites are associated with the cell membrane. The putative receptor for the zymogen exhibits low affinity for the ligand (dissociation constant of 0.38 microM and a high binding capacity (40,000 sites per cell). Plasminogen also binds in a cooperative fashion to type I collagen with an affinity which is higher than that displayed by cells. Collagen-bound plasminogen can be activated by cells preincubated with plasminogen in a manner that cells develop the capacity to adhere to type I collagen. The activation of collagen-bound plasminogen by cellular urokinase-like plasminogen activator (u-PA) was 60% more efficient than the activation of the soluble (not bound) form of plasminogen. These results suggest that in the invasive phenomena, WEHI cells operate as carriers of plasminogen from plasma to tissue. In addition, collagen can serve as a reservoir of zymogen in the extracellular matrix milieu through direct binding to plasminogen and at the same time allow more efficient plasminogen activation.