Erythromycin and clarithromycin modulation of growth factor-induced expression of heparanase mRNA on human lung cancer cells in vitro

Heparanase activity is correlated with the metastatic potential of several cancer cells and is a key enzyme in the breakdown of tissue barriers. It is also involved in the regulation of growth factor and cytokine activity. Ho wever, little is known about the factors that induce heparanase in cancer c ells. We investigated the effect of three growth factors, platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF) and basic fibroblast g rowth factor (bFGF), on heparanase mRNA induction in lung cancer cells in v itro. In addition, we examined the effect of erythromycin (EM) and clarithr omycin (CAM), which are 14-membered ring macrolide antibiotics that act as biological response modifiers, on the expression of heparanase mRNA induced by growth factors. PDGF, HGF and bFGF stimulated cell migration activity and enhanced the expr ession of heparanase mRNA in the human lung adenocarcinoma cell line A549. Via different mechanisms, EM and CAM modulate the induction by these factor s of heparanase mRNA expression on A549 cells. EM also significantly suppre ssed A549 cell migration induced by PDGF and HGF, and CAM significantly sup pressed A549 cell migration induced by bFGF. The results suggest that the growth factors PDGF, HGF and bFGF are importan t inducers of heparanase in potentially invasive and metastatic cancer cell s. The suppressive effect of heparanase mRNA expression by EM and CAM may h ave interesting therapeutic applications in the prevention of metastasis.