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

Thandokuhle Khumalo,Uwe Reusch,Melvyn Little,Stefan Knackmuss,Robin B Veale,Stefan F T Weiss,Corinne Ida Lasmezas

doi:10.1371/journal.pone.0066297

Thandokuhle Khumalo, Uwe Reusch + Show 5 more

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https://doi.org/10.1371/journal.pone.0066297

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Abstract

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.

Highlights

Cancer has become a global burden due to its high incidence and mortality rates, with metastasis held accountable for approximately 90% of cancer deaths
The interaction of laminin receptor precursor (LRP)/laminin receptor (LR) and laminin-1 on the cell surface of tumorigenic cells triggers the process of metastasis
A percentage was determined by calculating the difference between the respective cell line and the invasive potential of MCF-7 cell line. p-values were calculated using the two-tailed Students t-test with a 95%confidence interval. doi:10.1371/journal.pone.0066297.t001

Summary

Introduction

Cancer has become a global burden due to its high incidence and mortality rates, with metastasis held accountable for approximately 90% of cancer deaths. The 37-kDa/67-kDa laminin receptor (LRP/LR), a major receptor for extracellular matrix proteins, was first isolated from human breast carcinoma cells, murine melanoma cells [1] and normal muscle cells [2]. The relationship between the two isoforms, 37 kDa laminin receptor precursor and 67 kDa high affinity laminin receptor has not yet been encrypted but it is believed that the 37 kDa LRP isoform is the precursor of the 67kDa LR possibly through acylation or heterodimerisation [3] rather than homodimerisation [4]. On the cell surface the receptor serves as a receptor for laminin and acts as a co-receptor for elastin [10], carbohydrates [10] and the cellular prion protein [5,11]

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