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Growth inhibition of human mammary carcinoma by liposomal hexadecylphosphocholine: Participation of activated macrophages in the antitumor mechanism.
- Source :
-
International journal of cancer [Int J Cancer] 2001 May 01; Vol. 92 (3), pp. 426-33. - Publication Year :
- 2001
-
Abstract
- This study was undertaken to investigate the antitumor effect of liposomal hexadecylphosphocholine (L-HPC), a synthetic phospholipid encapsulated into multilamellar vesicles (MLV). The effect of these liposomes was tested in an orthotopic nude mouse model using the human mammary carcinomas MDA-MB 435 and 231. The main interest of the investigation was to study whether activated macrophages are substantially involved in the tumor growth inhibition mechanism. The growth of both MDA-MB 435 and 231 tumors in the mammary fat pad was significantly inhibited by a 14-day intraperitoneal therapy with L-HPC. The remaining tumors were shown to be heavily infiltrated with macrophages. 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 TNFalpha dependent but rather independent of IL-1alpha and nitric oxide (NO). NMA, a specific inhibitor of NO production, did not inhibit L-HPC-induced MMCTX. Furthermore, L-HPC was shown to upregulate the matrixmetalloproteinases MMP-9 and MMP-2 secretion into the supernatant. Considering cytokine release and production of collagenases, the L-HPC-induced macrophage activation cascade is assumed to be comparable with that of classical activators 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.<br /> (Copyright 2001 Wiley-Liss, Inc.)
- Subjects :
- Animals
Disease Models, Animal
Drug Carriers
Drug Delivery Systems
Humans
Interleukin-6 biosynthesis
Interleukin-6 genetics
Interleukin-6 immunology
Liposomes
Lymphocytes, Tumor-Infiltrating immunology
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 metabolism
Mice
Mice, Nude
Neoplasms, Experimental immunology
Neoplasms, Experimental metabolism
RNA, Messenger biosynthesis
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha biosynthesis
Tumor Necrosis Factor-alpha immunology
Xenograft Model Antitumor Assays
Antineoplastic Agents therapeutic use
Macrophage Activation drug effects
Neoplasms, Experimental drug therapy
Phosphorylcholine analogs & derivatives
Phosphorylcholine therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0020-7136
- Volume :
- 92
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 11291082
- Full Text :
- https://doi.org/10.1002/ijc.1201