Anti-LRP/LR specific antibody IgG1-iS18 impedes adhesion and invasion of liver cancer cells

PLoS One. 2014 May 5;9(5):e96268. doi: 10.1371/journal.pone.0096268. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Anti-Idiotypic / pharmacology*
  • Antibodies, Anti-Idiotypic / therapeutic use
  • Cell Adhesion*
  • Cell Line, Tumor
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / immunology
  • Laminin / metabolism
  • Leukemia / drug therapy
  • Leukemia / pathology*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology*
  • MCF-7 Cells
  • Neoplasm Invasiveness*
  • Receptors, Laminin / genetics
  • Receptors, Laminin / immunology
  • Receptors, Laminin / physiology*

Substances

  • Antibodies, Anti-Idiotypic
  • Immunoglobulin G
  • Laminin
  • Receptors, Laminin
  • laminin 1

Grants and funding

This work was supported by the National Research Foundation, the Republic of South Africa and the Medical Research Council, the Republic of South Africa. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s), and therefore, the National Research Foundation does not accept any liability in this regard thereto. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.