The Dual Inhibition of Met and EGFR by ME22S, a Novel Met/EGFR Bispecific Monoclonal Antibody, Suppresses the Proliferation and Invasion of Laryngeal Cancer

Lee, Bok‐Soon; Kim, Haeng-Jun; Hwang, Jae-Woong; Cheong, Kwang Ho; Kim, Kyung-Ah; Cha, Hyun-Young; Lee, Ji Min; Kim, Chul‐Ho

doi:10.1245/s10434-015-5084-0

Cited by 19 publications

(14 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Analogous data were acquired in 3D conditions, where cells invaded through the layer of the Matrigel. Similarly, Lee and coworkers showed that ME22S (a novel EGFR/MET bispecific antibody) significantly inhibited HGF‐stimulated migration and invasion of laryngeal carcinoma cells . Moreover, it was shown that down‐regulation of EGFR caused by MiR‐615 and MiR‐7, led to decreased migration, and invasion of human glioblastoma and ovarian cancer cells, respectively .…”

Section: Discussionmentioning

confidence: 90%

“…Similarly, Lee and coworkers showed that ME22S (a novel EGFR/MET bispecific antibody) significantly inhibited HGF-stimulated migration and invasion of laryngeal carcinoma cells. 35 Moreover, it was shown that down-regulation of EGFR caused by MiR-615 and MiR-7, led to decreased migration, and invasion of human glioblastoma and ovarian cancer cells, respectively. 36,37 Analogous effect was observed following MET silencing or its down-regulation in many cancers like ovarian cancer, breast cancer, hepatocellular cancer or gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells

Pietraszek-Gremplewicz

Simiczyjew

Dratkiewicz

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Epidermal and hepatocyte growth factors can stimulate invasive abilities of melanoma cells, while treatment with combination of their receptors' (EGFR and MET, respectively) inhibitors reduces viability of these cells, as we have previously shown. Proposed therapy has potential; however, used drugs block more than one goal effectively, what raises the question about the real target of analysed inhibitors. For this reason, we analysed direct involvement of these receptors in the invasion of melanoma cells inducing EGFR and MET up‐ and down‐regulations in examined cells. Results were acquired with assays evaluating cell migration and invasion (scratch wound assay, Transwell filter‐based method and single‐cell tracking). We revealed that cells' motile abilities are increased after EGFR overexpression and decreased following EGFR and MET silencing. This outcome correlates with elevated (EGFR up‐regulation) or reduced (EGFR/MET down‐regulation) number of formed invadopodia, visualized with immunofluorescence, and their rate of proteolytic abilities, evaluated by fluorescent gelatin degradation assay, and gelatin zymography, compared to control cells. Above‐mentioned data indicate that both—EGFR and MET signalling is directly connected with melanoma cells invasion, what establishes these receptors as promising targets for anti‐cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells

Pietraszek-Gremplewicz

Simiczyjew

Dratkiewicz

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…This kind of protein will give a reference for protein drugs in the treatment of human cancer in library and clinical practice. 31,32 In addition, hTERTR-FAM96A significantly promoted CTL responses and IFN-γ release by inducing tumor cells apoptosis in murine HCC models. Among many apoptosis-related molecules involving tumor cells apoptosis, we focused on Bcl-2, Brg-1, C-myc, Apo-1, Apaf-1, and Bax in hepatic carcinoma cells.…”

Section: Discussionmentioning

confidence: 96%

A multi-target protein of hTERTR-FAM96A presents significant anticancer potent in the treatment of hepatocellular carcinoma

Zhang

Wang

2017

Tumour Biol.

View full text Add to dashboard Cite

The abilities to escape apoptosis induced by anticancer drugs are an essential factor of carcinogenesis and a hallmark of resistance to cancer therapy. In this study, we identified hTERTR-FAM96A (human telomerase reverse transcriptasefamily with sequence similarity 96 member A) as a new efficient agent for apoptosome-activating and anti-tumor protein and investigated the potential tumor suppressor function in hepatocellular carcinoma. The hTERTR-FAM96A fusion protein was constructed by genetic engineering and its anticancer function of hTERTR-FAM96A was explored in vitro and in vivo by investigating the possible preclinical outcomes. Effects of hTERTR-FAM96A on improvement of apoptotic sensitivity and inhibition of migration and invasion were examined in cancer cells and tumors. Our results showed that the therapeutic effects of hTERTR-FAM96A were highly effective for inhibiting tumor growth and inducing apoptosis of hepatocellular carcinoma cells in H22-bearing nude mice. The hTERTR-FAM96A fusion protein could specifically bind with Apaf-1 and hTERT, which further induced apoptosis of hepatocellular carcinoma cells and improved apoptosis sensitivity. Our results indicated that hTERTR-FAM96A treatment enhanced cytotoxic effects by upregulation of cytotoxic T lymphocyte responses, interferon-γ release, and T lymphocyte infiltration. In addition, hTERTR-FAM96A led to tumor-specific immunologic cytotoxicity through increasing apoptotic body on hepatocellular tumors. Furthermore, hTERTR-FAM96A dramatically inhibited tumor growth, reduced death rate, and prolonged mice survival in hepatocellular carcinoma mice derived from three independent hepatocellular carcinoma mice cohorts compared to control groups. In summary, our data suggest that hTERTR-FAM96A may serve as an efficient anti-tumor agent for the treatment of hepatocellular carcinoma.

show abstract

“…In metastatic colorectal cancer, amplification and overexpression of MET is a key contributing factor to resistance to anti-EGFR therapies (Misale et al, 2014; Takahashi et al, 2016). Furthermore, dual inhibition of MET and EGFR by “biseptic” antibodies, or combined inhibitors, demonstrated effective inhibition of tumor growth in vitro and in vivo (Castoldi et al, 2013; Lee et al, 2016a; Xu et al, 2011), in accord with our findings in GC cluster B. Recently, another dual inhibition of MET and EGFR in GC cells has emerged, based on inhibition of sphingosine 1-phosphate (S1P), a G protein-coupled receptor ligand (Shida et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Cancer Transcriptome Dataset Analysis: Comparing Methods of Pathway and Gene Regulatory Network-Based Cluster Identification

Nam

2017

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

Cancer transcriptome analysis is one of the leading areas of Big Data science, biomarker, and pharmaceutical discovery, not to forget personalized medicine. Yet, cancer transcriptomics and postgenomic medicine require innovation in bioinformatics as well as comparison of the performance of available algorithms. In this data analytics context, the value of network generation and algorithms has been widely underscored for addressing the salient questions in cancer pathogenesis. Analysis of cancer trancriptome often results in complicated networks where identification of network modularity remains critical, for example, in delineating the “druggable” molecular targets. Network clustering is useful, but depends on the network topology in and of itself. Notably, the performance of different network-generating tools for network cluster (NC) identification has been little investigated to date. Hence, using gastric cancer (GC) transcriptomic datasets, we compared two algorithms for generating pathway versus gene regulatory network-based NCs, showing that the pathway-based approach better agrees with a reference set of cancer-functional contexts. Finally, by applying pathway-based NC identification to GC transcriptome datasets, we describe cancer NCs that associate with candidate therapeutic targets and biomarkers in GC. These observations collectively inform future research on cancer transcriptomics, drug discovery, and rational development of new analysis tools for optimal harnessing of omics data.

show abstract

The Dual Inhibition of Met and EGFR by ME22S, a Novel Met/EGFR Bispecific Monoclonal Antibody, Suppresses the Proliferation and Invasion of Laryngeal Cancer

Cited by 19 publications

References 27 publications

Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells

Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells

A multi-target protein of hTERTR-FAM96A presents significant anticancer potent in the treatment of hepatocellular carcinoma

Cancer Transcriptome Dataset Analysis: Comparing Methods of Pathway and Gene Regulatory Network-Based Cluster Identification

Contact Info

Product

Resources

About