Abstract
BackgroundCancer 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.MethodsAsPC-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.ResultsFlow 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.ConclusionThese 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.
Highlights
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 as a result of metastasis
We investigated whether the anti-laminin receptor precursor (LRP)/Laminin Receptor (LR) specific antibody immunoglobulin G1 (IgG1)-iS18 is capable of impeding the adhesive and invasive potential of pancreatic cancer (AsPC-1) and neuroblastoma (IMR-32) cells
Pancreatic cancer and neuroblastoma cells reveal laminin receptor precursor/ high affinity laminin receptor (LRP/LR) on the cell surface Cell surface LRP/LR was visualised in order to confirm that the tumorigenic cells did display LRP/LR on their surface and play a pivotal role in the occurrence of metastasis due to the LRP/LR- laminin-1 interaction
Summary
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 as a result of metastasis. Neuroblastoma most commonly affects infants and young children and it was ranked as the 17th most diagnosed cancer types in 2012 with approximately 256 000 cases being diagnosed [4]. Due to these alarming statistics, it is crucial to develop novel therapeutic strategies for the treatment of cancer and in particular metastatic pancreatic cancer and neuroblastoma
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