title: Anti-LRP/LR-specific antibody IgG1-iS18 impedes adhesion and invasion of pancreatic cancer and neuroblastoma cells.
abstract: Cancer has become a global burden due to its high incidence and mortality rates, with an estimated 14.1 million cancer cases reported worldwide in 2012 particularly as a result of metastasis. Metastasis involves two crucial steps: adhesion and invasion, and the non-integrin receptor; the 37-kDa/67-kDa laminin receptor precursor/ high affinity laminin receptor (LRP/LR) has been shown to be overexpressed on the surface of tumorigenic cells, thus being implicated in the enhancement of these two crucial steps. The current study investigated the role of LRP/LR on the aggressiveness of pancreatic cancer (AsPC-1) and neuroblastoma (IMR-32) cells with respect to their adhesive and invasive potential.
  
  
  
  AsPC-1 and IMR-32 cells were utilized as the experimental cell lines for the study. Cell surface LRP/LR levels were visualised and quantified on the experimental and control (MCF-7) cell lines via confocal microscopy and flow cytometry, respectively. Total LRP/LR levels in the cell lines were assessed by Western blotting and the adhesive and invasive potential of the above-mentioned cell lines was determined before and after supplementation with the anti-LRP/LR specific antibody IgG1-iS18. Statistical significance of the data was confirmed via the use of the two-tailed student's t-test and Pearson's correlation coefficient.
  
  
  
  Flow cytometry revealed that AsPC-1 and IMR-32 cells displayed significantly higher cell surface LRP/LR levels in comparison to the MCF-7 control cell line. However, Western blotting and subsequent densitometric analysis revealed that all three tumorigenic cell lines displayed no significant difference in total LRP/LR levels. The treatment of AsPC-1 and IMR-32 cells with IgG1-iS18 caused a significant reduction in the adhesive and invasive potential of the cells to laminin-1 and through the ECM-like Matrigel™, respectively. Pearson's correlation coefficients indicated a high correlation, thus suggesting a directly proportional relationship between cell surface LRP/LR levels and the adhesive and invasive potential of AsPC-1 and IMR-32 cells.
  
  
  
  These findings suggest that through the interference of the LRP/LR-laminin-1 interaction, the anti-LRP/LR specific antibody IgG1-iS18 may act as an alternative therapeutic tool for the treatment of metastatic pancreatic cancer and neuroblastoma.
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa (RSA).
authors.forename: Thalia M
authors.initials: TM
authors.lastname: Rebelo
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa (RSA).
authors.forename: Carryn J
authors.initials: CJ
authors.lastname: Chetty
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa (RSA).
authors.forename: Eloise
authors.initials: E
authors.lastname: Ferreira
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa (RSA). stefan.weiss@wits.ac.za.
authors.forename: Stefan F T
authors.initials: SF
authors.lastname: Weiss
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D012333:RNA, Messenger; D017474:Receptors, Laminin
keywords: 37 kDa/67-kDa laminin receptor (LRP/LR); Adhesion; Invasion; Laminin-1; Metastasis; Neuroblastoma; Pancreatic cancer