Anti-LRP/LR Specific Antibody IgG1-iS18 Impedes Adhesion and Invasion of Liver Cancer Cells

Chetty, Carryn J.; Khumalo, Thandokuhle; Dias, Bianca Da Costa; Reusch, Uwe; Knackmuss, Stefan; Little, Melvyn; Weiß, Stefan

doi:10.1371/journal.pone.0096268

Cited by 26 publications

(28 citation statements)

References 24 publications

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“…Previous studies have shown that the 67LR is associated with increased invasiveness in many different cancers 52, 53 and has been shown to increase cancer cell adhesion. 54 Thus, it is possible that the 67LR mediates 12Z multicellular cluster formation by promoting cell motility.…”

Section: Discussionmentioning

confidence: 99%

Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context

et al. 2014

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Endometriosis is a chronic disease in which epithelial and stromal cells that resemble the eutopic endometrium are found in ectopic lesions. In order to examine how microenvironmental factors such as extracellular matrix and macrophages influence disease progression, 12Z (an immortalized ectopic epithelial cell line) were cultured on tissue culture plastic (TCP) or in gels of recombinant basement membrane (rBM) or collagen I. Unlike cells in other conditions, cells in rBM formed multi-cellular structures in a 67 kDa non-integrin laminin receptor (67LR)-dependent manner. To examine the impact of macrophage-secreted factors on cell behavior, 12Z cells on all three substrates were treated with conditioned media from differentiated THP-1 (an immortalized monocytic cell line). Significant proliferation and invasion was observed only with cells cultured in rBM, indicating that extracellular matrix cues help dictate cell response to soluble signals. Cells cultured on rBM were then treated with individual cytokines detected in the conditioned media, with increased proliferation observed following exposure to interleukin-8 (CXCL8/IL-8) and both increased proliferation and invasion following treatment with heparin-binding EGF-like growth factor (HB-EGF). This study suggests that rBM gels can be used to induce in vitro lesion formation in order to identify soluble factors that influence proliferation and invasion.

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Section: Discussionmentioning

confidence: 99%

Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context

et al. 2014

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“…The 37-kDa LRP is thought to be the precursor of the 67-kDa high-affinity laminin receptor LR, however the exact mechanism by which the precursor forms the receptor is unknown [8]. The receptor is seen to be overexpressed on the surface of tumorigenic cells such as cervical, lung, prostate and colon [9, 10], breast and oesophageal [11] and liver cancer cells [12], thus serving many physiological functions such as signal transduction, cell cycle progression, cell migration, cell-matrix adhesion, cell viability and proliferation [13–15]. LRP/LR is also associated with the process of Aβ- generation in Alzheimer’s disease [16, 17] as well as enhancing telomerase activity which is seen to play a role in disease progression and chemotherapy resistance in some cancers [18].…”

Section: Introductionmentioning

confidence: 99%

“…It is a monoclonal anti-LRP/LR specific antibody which was designed to specifically target the LRP/LR-laminin-1 interaction and it is characteristic of having a high stability and long half-life of up to 21 days in blood. This approach has therefore been shown to significantly reduce the adhesive and invasive potential of several tumorigenic cells [10–12]. …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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“…While LRP/LR predominantly functions as a transmembrane receptor (8), it has also been found in the nucleus, where it interacts with histones and chromatin (9), as well as in the cytosol, where it aids in translation and ribosomal deaths (http://www.wcrf.org/int/ cancer-facts-figures/worldwide-data). Untreated colorectal cancer is the second most fatal type after lung cancer, yet if diagnosed in its early stages, it can be effectively treated (2).…”

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confidence: 99%

“…This increased interaction subsequently leads to increased adhesion, followed by activation of Type IV collagenase, leading to degradation of the basement membrane and invasion by the tumorigenic cells (28). Overexpression of LRP/LR, when compared with noninvasive tumorigenic cells, has been observed in various invasive tumors, including pancreatic cancer cells (29); colon, lung, prostate and cervical cancer cells (30); esophageal and breast cancer cells (31); and liver cancer cells (8).…”

mentioning

confidence: 99%

Anti-LRP/LR-Specific Antibody IgG1-iS18 Significantly Impedes Adhesion and Invasion in Early- and Late-Stage Colorectal Carcinoma Cells

Vania

Chetty

Ferreira

et al. 2016

Mol Med

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Cancer is a highly complex disease that has become one of the leading causes of death globally. Metastasis, a major cause of cancer deaths, requires two crucial events, adhesion and invasion. The 37kDa/67kDa laminin receptor (laminin receptor precursor/high-affinity laminin receptor [LRP/LR]) enhances these two steps, consequently aiding in cancer progression. In this study, the role of LRP/LR in adhesion and invasion of early-stage (SW-480 and HT-29) and late-stage (DLD-1) colorectal cancer cells was investigated. Western blotting revealed that early-and late-stage colorectal cancer cells contained significantly higher total LRP/LR levels compared with poorly invasive MCF-7 breast cancer control cells. Flow cytometry revealed that both stages of colorectal cancer displayed significantly higher cell surface LRP/LR levels. Furthermore, upon treatment of colorectal cancer cells with the anti-LRP/LR-specific antibody IgG1-iS18, adhesion to laminin-1 was significantly reduced in both stages. Each stage's invasive potential was determined using the Matrigel™ invasion assay, showing that invasion was significantly impeded in both colorectal cancer stages when the cells were incubated with IgG1-iS18. In addition, Pearson's correlation coefficients propose that both total and cell surface LRP/LR levels are directly proportional to the adhesive and invasive potential of both stages of colorectal cancer. Hence, these findings indicate potential for use of the IgG1-iS18 antibody as a promising therapeutic tool for colorectal cancer patients at both stages.

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Anti-LRP/LR Specific Antibody IgG1-iS18 Impedes Adhesion and Invasion of Liver Cancer Cells

Cited by 26 publications

References 24 publications

Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context

Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context

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

Anti-LRP/LR-Specific Antibody IgG1-iS18 Significantly Impedes Adhesion and Invasion in Early- and Late-Stage Colorectal Carcinoma Cells

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