Critical role for matrix metalloproteinase‐9 in platelet‐activating factor‐induced experimental tumor metastasis

In this study, the roles of matrix metalloproteinase (MMP)‐2 and MMP‐9 in platelet‐activating factor (PAF)‐induced experimental pulmonary metastasis of the murine melanoma cell, B16F10, were investigated. An injection of PAF resulted in increases in mRNA expression, protein levels and the activities of both MMP‐2 and MMP‐9 in the lungs. The overall expression of MMP‐9 was stronger than that of MMP‐2. The increased MMP‐9 expression was inhibited by both NF‐κB and AP‐1 inhibitors, whereas the increased MMP‐2 expression was inhibited by only AP‐1 inhibitors. Immunohistochemical analysis revealed that MMP‐9 was expressed in bronchial epithelial cells as well as in the walls of blood vessels, whereas MMP‐2 expression was observed only in bronchial epithelial cells. PAF significantly enhanced the pulmonary metastasis of B16F10, which was inhibited by both NF‐κB and c‐jun inhibitors. MMP‐9 inhibitor, but not that of MMP‐2, completely inhibited PAF‐induced B16F10 metastasis. These data indicate that MMP‐9, the expression of which was regulated by NF‐κB and AP‐1, plays a critical role in PAF‐induced enhancement of pulmonary melanoma metastasis. © 2006 Wiley‐Liss, Inc.