Combination of EGFR inhibitor lapatinib and MET inhibitor foretinib inhibits migration of triple negative breast cancer cell lines
- Author
- Aleksandra Simiczyjew, Ewelina Dratkiewicz, Marleen Van Troys (UGent) , Christophe Ampe (UGent) , Ilona Styczeń and Dorota Nowak
- Organization
- Abstract
- Triple-negative breast cancer (TNBC) is the most challenging subtype to treat due to the lack of estrogen receptor, progesterone receptor, and HER2 expression, which excludes the usage of directed targeted therapy against them. Promising therapeutic targets are the hepatocyte growth factor receptor (MET) and epidermal growth factor receptor (EGFR), which expression is frequently elevated in TNBC. Inhibitors of these receptors used as monotherapy are often ineffective. Due to that, we studied the efficacy of combined therapy targeting MET and EGFR simultaneously. Two TNBC cell lines were treated with lapatinib (a dual EGFR and HER2 inhibitor), foretinib (a MET inhibitor), or a combination of the two. After the inhibitors treatment, we verified the cell viability (XTT assay), distribution of the cell cycle phases, the activation of signaling pathways (Western blotting), distribution of invadopodia, fluorescent gelatin digestion (immunofluorescence), and the invasion capacity of cells. A combination of foretinib and lapatinib effectively reduced the viability of examined cells, led to G2/M arrest and reduction of pAKT. There was also a decrease in number of invadopodia formed by cells, their ability to digest gelatin and reduction of cells migration/invasion capacity. Therapy targeting of both EGFR and MET receptors was much more effective against tested cells than monotherapy. We selected a combination of drugs that could be successfully used against this breast cancer subtype.
- Keywords
- receptor tyrosine kinases, EGFR, MET, RTK inhibitors, triple negative breast cancer, GROWTH-FACTOR RECEPTOR, LUNG-CANCER, RESISTANCE, AMPLIFICATION, INVADOPODIA, ACTIVATION, EXPRESSION, PROTEINS, THERAPY, TARGET
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8582277
- MLA
- Simiczyjew, Aleksandra, et al. “Combination of EGFR Inhibitor Lapatinib and MET Inhibitor Foretinib Inhibits Migration of Triple Negative Breast Cancer Cell Lines.” CANCERS, vol. 10, no. 9, 2018, doi:10.3390/cancers10090335.
- APA
- Simiczyjew, A., Dratkiewicz, E., Van Troys, M., Ampe, C., Styczeń, I., & Nowak, D. (2018). Combination of EGFR inhibitor lapatinib and MET inhibitor foretinib inhibits migration of triple negative breast cancer cell lines. CANCERS, 10(9). https://doi.org/10.3390/cancers10090335
- Chicago author-date
- Simiczyjew, Aleksandra, Ewelina Dratkiewicz, Marleen Van Troys, Christophe Ampe, Ilona Styczeń, and Dorota Nowak. 2018. “Combination of EGFR Inhibitor Lapatinib and MET Inhibitor Foretinib Inhibits Migration of Triple Negative Breast Cancer Cell Lines.” CANCERS 10 (9). https://doi.org/10.3390/cancers10090335.
- Chicago author-date (all authors)
- Simiczyjew, Aleksandra, Ewelina Dratkiewicz, Marleen Van Troys, Christophe Ampe, Ilona Styczeń, and Dorota Nowak. 2018. “Combination of EGFR Inhibitor Lapatinib and MET Inhibitor Foretinib Inhibits Migration of Triple Negative Breast Cancer Cell Lines.” CANCERS 10 (9). doi:10.3390/cancers10090335.
- Vancouver
- 1.Simiczyjew A, Dratkiewicz E, Van Troys M, Ampe C, Styczeń I, Nowak D. Combination of EGFR inhibitor lapatinib and MET inhibitor foretinib inhibits migration of triple negative breast cancer cell lines. CANCERS. 2018;10(9).
- IEEE
- [1]A. Simiczyjew, E. Dratkiewicz, M. Van Troys, C. Ampe, I. Styczeń, and D. Nowak, “Combination of EGFR inhibitor lapatinib and MET inhibitor foretinib inhibits migration of triple negative breast cancer cell lines,” CANCERS, vol. 10, no. 9, 2018.
@article{8582277,
abstract = {{Triple-negative breast cancer (TNBC) is the most challenging subtype to treat due to the lack of estrogen receptor, progesterone receptor, and HER2 expression, which excludes the usage of directed targeted therapy against them. Promising therapeutic targets are the hepatocyte growth factor receptor (MET) and epidermal growth factor receptor (EGFR), which expression is frequently elevated in TNBC. Inhibitors of these receptors used as monotherapy are often ineffective. Due to that, we studied the efficacy of combined therapy targeting MET and EGFR simultaneously. Two TNBC cell lines were treated with lapatinib (a dual EGFR and HER2 inhibitor), foretinib (a MET inhibitor), or a combination of the two. After the inhibitors treatment, we verified the cell viability (XTT assay), distribution of the cell cycle phases, the activation of signaling pathways (Western blotting), distribution of invadopodia, fluorescent gelatin digestion (immunofluorescence), and the invasion capacity of cells. A combination of foretinib and lapatinib effectively reduced the viability of examined cells, led to G2/M arrest and reduction of pAKT. There was also a decrease in number of invadopodia formed by cells, their ability to digest gelatin and reduction of cells migration/invasion capacity. Therapy targeting of both EGFR and MET receptors was much more effective against tested cells than monotherapy. We selected a combination of drugs that could be successfully used against this breast cancer subtype.}},
articleno = {{335}},
author = {{Simiczyjew, Aleksandra and Dratkiewicz, Ewelina and Van Troys, Marleen and Ampe, Christophe and Styczeń, Ilona and Nowak, Dorota}},
issn = {{2072-6694}},
journal = {{CANCERS}},
keywords = {{receptor tyrosine kinases,EGFR,MET,RTK inhibitors,triple negative breast cancer,GROWTH-FACTOR RECEPTOR,LUNG-CANCER,RESISTANCE,AMPLIFICATION,INVADOPODIA,ACTIVATION,EXPRESSION,PROTEINS,THERAPY,TARGET}},
language = {{eng}},
number = {{9}},
pages = {{17}},
title = {{Combination of EGFR inhibitor lapatinib and MET inhibitor foretinib inhibits migration of triple negative breast cancer cell lines}},
url = {{http://doi.org/10.3390/cancers10090335}},
volume = {{10}},
year = {{2018}},
}
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