Growth inhibition of human mammary carcinoma by liposomal hexadecylphosphocholine: Participation of activated macrophages in the antitumor mechanism

This study was undertaken to investigate the antitumor effect of liposomal hexadecylphosphocholine (L-H PC), a synthetic phospholipid encapsulated int o multilamellar vesicles (MLV), The effect of these liposomes was tested in an orthotopic nude mouse model using the human mammary carcinomas MDA-MB 4 35 and 231, The main interest of the investigation was to study whether act ivated macrophages are substantially involved in the tumor growth inhibitio n mechanism. The growth of both MDA-MB 435 and 231 tumors in the mammary fa t pad was significantly inhibited by a I Ii-day intraperitoneal therapy wit h L-HPC. The remaining tumors were shown to be heavily infiltrated with mac rophages. In vitro studies of mPEM demonstrated a significant induction of macrophage-mediated tumor cytotoxicity (MMCTX) against the 2 cell lines by L-HPC, The L-HPC-mediated activation mechanism was characterized to be IL-6 and TNF alpha dependent but rather independent of IL-1 alpha and nitric ox ide (NO), NMA, a specific inhibitor of NO production, did not inhibit L-HPC -induced MMCTX, Furthermore, L-HPC was shown to upregulate the matrixmetall oproteinases MMP-9 and MMP-2 secretion into the supernatant. Considering cy tokine release and production of collagenases, the L-HPC-induced macrophage activation cascade is assumed to be comparable with that of classical acti vators such as lipopolysaccharide (LPS) and interferon (IFN) gamma, As far as NO production is considered, the L-HPC activation mechanism differs from that caused by LPS and IFN gamma. (C) 2001 Wiley-Liss. Inc.