title: Anti-LRP/LR specific antibody IgG1-iS18 impedes adhesion and invasion of liver cancer cells.
abstract: Two key events, namely adhesion and invasion, are pivotal to the occurrence of metastasis. Importantly, the 37 kDa/67 kDa laminin receptor (LRP/LR) has been implicated in enhancing these two events thus facilitating cancer progression. In the current study, the role of LRP/LR in the adhesion and invasion of liver cancer (HUH-7) and leukaemia (K562) cells was investigated. Flow cytometry revealed that the HUH-7 cells displayed significantly higher cell surface LRP/LR levels compared to the poorly-invasive breast cancer (MCF-7) control cells, whilst the K562 cells displayed significantly lower cell surface LRP/LR levels in comparison to the MCF-7 control cells. However, Western blotting and densitometric analysis revealed that all three tumorigenic cell lines did not differ significantly with regards to total LRP/LR levels. Furthermore, treatment of liver cancer cells with anti-LRP/LR specific antibody IgG1-iS18 (0.2 mg/ml) significantly reduced the adhesive potential of cells to laminin-1 and the invasive potential of cells through the ECM-like Matrigel, whilst leukaemia cells showed no significant differences in both instances. Additionally, Pearson's correlation coefficients suggested direct proportionality between cell surface LRP/LR levels and the adhesive and invasive potential of liver cancer and leukaemia cells. These findings suggest the potential use of anti-LRP/LR specific antibody IgG1-iS18 as an alternative therapeutic tool for metastatic liver cancer through impediment of the LRP/LR- laminin-1 interaction.
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Gauteng, The Republic of South Africa (RSA).
authors.forename: Carryn
authors.initials: C
authors.lastname: Chetty
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Gauteng, The Republic of South Africa (RSA).
authors.forename: Thandokuhle
authors.initials: T
authors.lastname: Khumalo
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Gauteng, The Republic of South Africa (RSA).
authors.forename: Bianca
authors.initials: B
authors.lastname: Da Costa Dias
authors.affiliation: Affimed Therapeutics AG, Technologiepark, Im Neuenheimer Feld, Heidelberg, Baden-Wuerttemberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Reusch
authors.affiliation: Affimed Therapeutics AG, Technologiepark, Im Neuenheimer Feld, Heidelberg, Baden-Wuerttemberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knackmuss
authors.affiliation: Affimed Therapeutics AG, Technologiepark, Im Neuenheimer Feld, Heidelberg, Baden-Wuerttemberg, Germany.
authors.forename: Melvyn
authors.initials: M
authors.lastname: Little
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Gauteng, The Republic of South Africa (RSA).
authors.forename: Stefan F T
authors.initials: SF
authors.lastname: Weiss
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007797:Laminin / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D017474:Receptors, Laminin / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D007797:Laminin; D017474:Receptors, Laminin; C121346:laminin 1