title: Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level.
abstract: Trastuzumab (Herceptin) targets the human epidermal growth factor receptor 2 (HER2), which is overexpressed in 20-30% of breast and ovarian cancers carrying a bad prognosis. Our purpose was to target HER2-overexpressing human breast cancer cells with pegylated immunoliposomes bearing trastuzumab and containing melittin, which has recently shown anticancer properties. Using a panel of human breast cancer cells with different HER2 expression levels, these immunoliposomes decreased cancer cells viability in a dose-response manner and in correlation to their level of HER2 expression. Specific binding of the immunoliposomes to SKBr3 breast cancer cells was shown by ImageStream-based analysis. The morphological changes observed in the treated cells suggested a cytolytic process. This preclinical approach may suppose an effective strategy for the treatment of HER2-overexpressing tumors, and can support the development of an early phases I-II clinical trial. Trastuzumab resistant breast cancer cells (JIMT-1), can also be targeted using this approach.
authors.affiliation: Molecular and Cellular Biology Institute, Miguel Hernández University, Alicante, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Barrajón-Catalán
authors.forename: María P
authors.initials: MP
authors.lastname: Menéndez-Gutiérrez
authors.forename: Alberto
authors.initials: A
authors.lastname: Falco
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Miguel
authors.initials: M
authors.lastname: Saceda
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008081:Liposomes; D008555:Melitten / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008081:Liposomes; D008555:Melitten; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab