P0 protein mediated targeting of liposomes to melanoma cells with high level of ICAM-1 expression.

The feasibility of targeting liposomes reconstituted with P0 protein (P0-liposomes) to melanoma cells with high level of intercellular adhesion molecule-1 (ICAM-1) expression was investigated. P0 protein, an immunoglobulin superfamily (IgSF) cell adhesion molecule from peripheral nerve myelin, was used as a model targeting ligand. Liposome uptake by the cells was quantitated using radioactive lipids. The presence of intact P0 protein in the liposome bilayer increased the extent of interaction of liposomes with human M21 (7.80 fold) and A-375 (4.62 fold) melanoma cells compared to control liposomes of same lipid composition but no P0 protein, whereas with MeM 50-10 melanoma cells no significant increase was found (1.70 fold). The extent of binding of P0-liposomes to the melanoma cells correlated with the level of ICAM-1 expression on cells (r2 = 0.9996). M21 and A-375 cells express ICAM-1 (the percentage of stained cells, PSC, was 95% and 85%, respectively), whereas, MeM 50-10 cells do not. P0 protein also increased the interaction of liposomes with P0 protein expressing CHO-X2 cells (4.36 fold, as a positive control) compared to control liposomes. The indirect flow cytometry experiments using biotinylated P0 protein showed that P0 protein itself in solution also binds to M21 cells but does not bind to MeM 50-10 cells. Preincubation of M21 cells with anti-ICAM-1 monoclonal antibody decreased the binding of biotinylated P0 protein to the M21 cells by 35%. P0 protein or its binding domain(s) that mediate the targeting of liposomes through adhesive interactions may be useful for the development of novel types of drug delivery systems. This approach may have relevance in the treatment of metastatic cancers, inflammation and viral diseases, where cell adhesion proteins are over expressed.

[1]  Soldano Ferrone,et al.  Clinical Significance of αvβ3 Integrin and Intercellular Adhesion Molecule-1 Expression in Cutaneous Malignant Melanoma Lesions , 1997 .

[2]  John W. Park,et al.  Sterically stabilized anti-HER2 immunoliposomes: design and targeting to human breast cancer cells in vitro. , 1997, Biochemistry.

[3]  W. Hendrickson,et al.  Crystal Structure of the Extracellular Domain from P0, the Major Structural Protein of Peripheral Nerve Myelin , 1996, Neuron.

[4]  S. Ferrone,et al.  Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma. , 1993, Cancer research.

[5]  M. Maio,et al.  Differential expression of cell adhesion molecules CD54/CD11a and CD58/CD2 by human melanoma cells and functional role in their interaction with cytotoxic cells. , 1993, Cancer research.

[6]  C. Scheibenbogen,et al.  Differential expression and release of LFA‐3 and ICAM‐1 in human melanoma cell lines , 1993, International journal of cancer.

[7]  C A Buck,et al.  Immunoglobulin superfamily: structure, function and relationship to other receptor molecules. , 1992, Seminars in cell biology.

[8]  M. Foldvari,et al.  Intracellular delivery of drugs by liposomes containing P0 glycoprotein from peripheral nerve myelin into human M21 melanoma cells. , 1991, Journal of pharmaceutical sciences.

[9]  M. Tahara,et al.  Isolation and sequence determination of cDNA encoding the major structural protein of human peripheral myelin. , 1991, Biochemical and biophysical research communications.

[10]  M. Schachner,et al.  Recombinant peripheral myelin protein Po confers both adhesion and neurite outgrowth‐promoting properties , 1990, Journal of neuroscience research.

[11]  F. Ferrara,et al.  Differential expression of CD54/intercellular adhesion molecule-1 in myeloid leukemias and in lymphoproliferative disorders. , 1990, Blood.

[12]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[13]  B. Trapp,et al.  Role of myelin Po protein as a homophilic adhesion molecule , 1990, Nature.

[14]  P. Brophy,et al.  Protein zero of peripheral nerve myelin: Biosynthesis, membrane insertion, and evidence for homotypic interaction , 1990, Neuron.

[15]  S. Ferrone,et al.  Differential expression of intercellular adhesion molecule 1 in primary and metastatic melanoma lesions. , 1990, Cancer research.

[16]  M. Foldvari,et al.  Reconstitution into liposomes of highly purified PO glycoprotein from avian peripheral nerve myelin , 1990 .

[17]  M. Barbu Molecular cloning of cDNAs that encode the chicken Po protein: Evidence for early expression in avians , 1990, Journal of neuroscience research.

[18]  Michael Loran Dustin,et al.  Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families , 1988, Cell.

[19]  G. Lemke,et al.  Isolation and analysis of the gene encoding peripheral myelin protein zero , 1988, Neuron.

[20]  Timothy A. Springer,et al.  Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen 1 (LFA-1) , 1987, Cell.

[21]  K. Uyemura,et al.  Structure of P0 protein: Homology to immunoglobulin superfamily , 1987 .

[22]  K. Brunden,et al.  Isolation of an integral membrane glycoprotein by chloroform-methanol extraction and C3-reversed-phase high-performance liquid chromatography. , 1987, Analytical biochemistry.

[23]  Michael Loran Dustin,et al.  Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). , 1986, Journal of immunology.

[24]  G. Blobel,et al.  The receptor for transepithelial transport of IgA and IgM contains multiple immunoglobulin-like domains , 1984, Nature.

[25]  J. Verpoorte,et al.  The PO Protein of Chick Sciatic Nerve Myelin: Purification and Partial Characterization , 1982, Journal of neurochemistry.

[26]  M. W. Roomi,et al.  The PO protein. The major glycoprotein of peripheral nerve myelin. , 1978, Biochimica et biophysica acta.

[27]  M. Jaafari,et al.  Targeting liposomes through immunoglobulin superfamily domains: P0 protein as a model. , 1998, Drug delivery.

[28]  H. Gabius,et al.  Studies on carbohydrate-binding proteins using liposome-based systems--I. Preparation of neoglycoprotein-conjugated liposomes and the feasibility of their use as drug-targeting devices. , 1992, The International journal of biochemistry.

[29]  G. Riethmüller,et al.  De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[30]  G. L. Peterson [12] Determination of total protein , 1983 .

[31]  G. Edelman,et al.  Binding properties of a cell adhesion molecule from neural tissue. , 1982, Proceedings of the National Academy of Sciences of the United States of America.