Adhesion and Invasion of Breast and Oesophageal Cancer Cells Are Impeded by Anti-LRP/LR-Specific Antibody IgG1-iS18

Adhesion and invasion have been identified as the two key components of metastasis. The 37 kDa/67 kDa laminin receptor (LRP/LR) is thought to enhance these two processes thus endorsing the progression of cancer. Here we report on LRP/LR and the metastatic potential of MDA-MB 231 breast and WHCO1 oes...

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Bibliographic Details
Published inPloS one Vol. 8; no. 6; p. e66297
Main Authors Khumalo, Thandokuhle, Reusch, Uwe, Knackmuss, Stefan, Little, Melvyn, Veale, Robin B, Weiss, Stefan F T
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 18.06.2013
Public Library of Science (PLoS)
Subjects
Adhesion
Analysis
Angiogenesis
Antibodies - immunology
Apoptosis
Biology
Breast cancer
Breast Neoplasms - pathology
Cancer
Cancer cells
Cancer metastasis
Cell adhesion
Cell Adhesion - immunology
Cell Line, Tumor
Cell surface
Cervical cancer
Colorectal cancer
Correlation
Correlation coefficient
Correlation coefficients
Cytometry
Development and progression
Esophageal cancer
Esophageal Neoplasms - pathology
Esophagus
Extracellular matrix
Female
Flow cytometry
Gene expression
Health aspects
Humans
Immunoglobulin G
Immunoglobulin G - immunology
Immunoglobulins
Laminin
Lung cancer
Male
Medical research
Medicine
Metastases
Metastasis
Neoplasm Invasiveness - immunology
Prostate cancer
Proteins
Receptors, Laminin - immunology
Rodents
Tumors
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Summary:Adhesion and invasion have been identified as the two key components of metastasis. The 37 kDa/67 kDa laminin receptor (LRP/LR) is thought to enhance these two processes thus endorsing the progression of cancer. Here we report on LRP/LR and the metastatic potential of MDA-MB 231 breast and WHCO1 oesophageal cancer cells. Western blot analysis revealed a significant increase in total laminin receptor precursor (LRP) levels of breast and oesophageal cancer cells in comparison to non-invasive MCF-7 breast cancer cells, whereas LRP/LR cell surface levels in both cell lines were not significantly different to those of MCF-7 cells as analysed by flow cytometry. Incubation of breast and oesophageal cancer cells with the anti-LRP/LR specific antibody, IgG1-iS18, resulted in significant reduction in the adhesive potential of WHCO1 and MDA-MB 231 cells by 92% and 16%, respectively. Moreover, invasion was significantly impeded by 98% and 25% for WHCO1 and MDA-MB 231 cells, respectively. Pearson's correlation coefficients proved a positive correlation between total LRP/LR levels and invasive potential as well as between the adhesive and invasive potential of breast and oesophageal cancer cells. Our findings suggest that through interference of the LRP/LR-laminin-1 interaction, anti-LRP/LR specific antibody IgG1-iS18 may act as a possible alternative therapeutic tool for metastatic breast and oesophageal cancer treatment.
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Competing Interests: SFTW is currently a PLOS ONE Editorial Board Member. UR, SK and ML are affiliated with or employed by Affimed Therapeutics AG, a commercial company which produces therapeutic antibodies for the treatment of cancer and inflammatory diseases. Furthermore, the anti-LRP/LR antibodies used in this study for the blockade of angiogenesis have been described in two international patents as potential therapeutic anticancer tools. Namely patent, EP0984987, entitled “A soluble laminin receptor precursor and methods to inhibit its interactions” has claims directed to a pharmaceutical composition comprising a soluble laminin receptor precursor or functional derivative or fragment thereof and is owned by the University of the Witwatersrand. This patent has been validated in the United Kingdom and Germany. The second patent, EP1670826, is co-owned by the University of the Witwatersrand and Affimed Therapeutics AG and is entitled “Singlechain antibody acting against 37 kDa/67 kDa laminin receptor as tools for the diagnosis and therapy of prion diseases and cancer, production and use thereof”. This granted European patent was validated in the United Kingdom, France, Germany, Switzerland and Austria. The claims are directed to a single chain antibody molecule specifically targeting LRP/LR for the treatment of prion diseases or cancer. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: SFTW RV. Performed the experiments: TK. Analyzed the data: TK. Contributed reagents/materials/analysis tools: UR SK ML. Wrote the paper: TK. Revised manuscript: SFTW RV.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0066297