Modulation of Plasminogen Activation and Type IV Collagenase Activity by a Synthetic Peptide Derived From the Laminin A Chain.

Laminin is a large multidomain glycoprotein with diverse biological activities which include stimulation of neurite outgrowth,enhancement of tumor metastasis,and promotion of cell growth,adhesion,and differentiation. A 19 amino acid synthetic peptide derived from the ES fragment of the laminin A chain (Cys-Ser-Arg-A la-Arg-Lys-Gln-Ala-Ala-Ser- Ile-Lys-Val-Ala-Val-Ser-Ala-Asp-Arg-N H2) was identified which promotes metastasis and stimulates collagenase IV activity in the culture medium of B16 melanoma cells (Kanemoto et al.,1990). We report that this peptide,here designated LamA209- 1 2108,is also a potent stimulator of tissue plasminogen activator (t-PA)-catalyzed plasminogen activation,resulting in a 22-fold increase in the kcai/ Km of the activation reaction. The activity of purified type I and type IV collagenase was inhibited by LamAo2 9 1-2iso with IC 50 values of 3 and 43 µM,respectively. These data support an alternative mechanism for the appearance of collagenase activity in the culture media of melanoma cells,namely,that the peptide stimulates plasminogen activation,subsequently generating collagenase activity.