Modulation of matrix metalloproteinase-9 activity by hyaluronan is dependent on NF-κB activity in lymphoma cell lines with dissimilar invasive behavior

Abstract

Expression and activity of matrix metalloproteinase-9 (MMP-9) as well as its relationship with hyaluronan (HA) and NF-κB activity were analyzed in two murine lymphoma cell lines with dissimilar migration and invasive behavior. MMP activity was evaluated by zymograms in supernatants, membrane extracts of tumor cells, and in the organs invaded by these cells. The more aggressive LBLa cell line showed MMP-9 activity in vitro, which increased after HA treatment and was blocked by anti-CD44 mAb. Such activity was not found in the less aggressive LBLc. MMP-9 and MMP-2 activity was found in organs invaded by both cell lines, although differential MMP-9 activity was observed in lung infiltrated only by LBLa cell line. NF-κB activation was evaluated to determine whether differential activity of MMP-9 was dependent on downstream signaling pathway, showing higher NF-κB activity in the more aggressive LBLa cell line. Our results showed that MMP-9 activity modulated by HA through NF-κB signaling pathway may be involved in the aggressive behavior of LBLa.