Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF
Mauro Sousa de Almeida,1 Arya Roshanfekr,1 Sandor Balog,1 Alke Petri-Fink,1,2 Barbara Rothen-Rutishauser1 1Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland; 2Department of Chemistry, University of Fribourg, Fribourg, SwitzerlandCorrespondence: Barbara Rothen-Rutishauser, Adolp...
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Dove Medical Press
2023-02-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/cellular-uptake-of-silica-particles-influences-egfr-signaling-pathway--peer-reviewed-fulltext-article-IJN |
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| author | Sousa de Almeida M Roshanfekr A Balog S Petri-Fink A Rothen-Rutishauser B |
| author_facet | Sousa de Almeida M Roshanfekr A Balog S Petri-Fink A Rothen-Rutishauser B |
| author_sort | Sousa de Almeida M |
| collection | DOAJ |
| description | Mauro Sousa de Almeida,1 Arya Roshanfekr,1 Sandor Balog,1 Alke Petri-Fink,1,2 Barbara Rothen-Rutishauser1 1Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland; 2Department of Chemistry, University of Fribourg, Fribourg, SwitzerlandCorrespondence: Barbara Rothen-Rutishauser, Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland, Email barbara.rothen@unifr.chBackground: The human epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is involved in several key cellular processes, such as cell proliferation and differentiation, and it has been linked to the development and progression of various cancers (e.g., breast and lung). Researchers have attempted to improve current cancer-targeted therapies by conjugating molecules on the surface of (nano)particles to efficiently target and inhibit EGFR. However, very few in vitro studies have investigated the effect of particles per se on EGFR signaling and dynamics. Furthermore, the impact of concomitant exposure of particles and EGFR ligands, such as epidermal growth factor (EGF) on cellular uptake efficiency has received little attention.Purpose: The purpose of this research was to determine the effects of silica (SiO2) particles on EGFR expression and intracellular signaling pathways in A549 lung epithelial cells, in the presence or absence of epidermal growth factor (EGF).Results: We showed that A549 cells are able to internalize SiO2 particles with core diameters of 130 nm and 1 μm without affecting cell proliferation or migration. However, both SiO2 particles interfere with the EGFR signaling pathway by raising the endogenous levels of extracellular signal-regulated kinase (ERK) 1/2. Furthermore, both in the presence and absence of SiO2 particles, the addition of EGF increased cell migration. EGF also stimulated cellular uptake of 130 nm SiO2 particles but not 1 μm particles. The increased uptake is primarily associated with EGF-stimulated macropinocytosis.Conclusion: This study shows that SiO2 particle uptake interferes with cellular signaling pathways and can be boosted by concurrent exposure to the bioactive molecule EGF. SiO2 particles, both alone and in combination with the ligand EGF, interfere with EGFR signaling pathway in a size-dependent manner.Keywords: endocytosis, nanoparticles, epidermal growth factor, cellular signaling |
| first_indexed | 2024-04-10T07:09:27Z |
| format | Article |
| id | doaj.art-85b7abfec251484faa5d43ea433992e8 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-04-10T07:09:27Z |
| publishDate | 2023-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-85b7abfec251484faa5d43ea433992e82023-02-26T15:41:34ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-02-01Volume 181047106181874Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGFSousa de Almeida MRoshanfekr ABalog SPetri-Fink ARothen-Rutishauser BMauro Sousa de Almeida,1 Arya Roshanfekr,1 Sandor Balog,1 Alke Petri-Fink,1,2 Barbara Rothen-Rutishauser1 1Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland; 2Department of Chemistry, University of Fribourg, Fribourg, SwitzerlandCorrespondence: Barbara Rothen-Rutishauser, Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland, Email barbara.rothen@unifr.chBackground: The human epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is involved in several key cellular processes, such as cell proliferation and differentiation, and it has been linked to the development and progression of various cancers (e.g., breast and lung). Researchers have attempted to improve current cancer-targeted therapies by conjugating molecules on the surface of (nano)particles to efficiently target and inhibit EGFR. However, very few in vitro studies have investigated the effect of particles per se on EGFR signaling and dynamics. Furthermore, the impact of concomitant exposure of particles and EGFR ligands, such as epidermal growth factor (EGF) on cellular uptake efficiency has received little attention.Purpose: The purpose of this research was to determine the effects of silica (SiO2) particles on EGFR expression and intracellular signaling pathways in A549 lung epithelial cells, in the presence or absence of epidermal growth factor (EGF).Results: We showed that A549 cells are able to internalize SiO2 particles with core diameters of 130 nm and 1 μm without affecting cell proliferation or migration. However, both SiO2 particles interfere with the EGFR signaling pathway by raising the endogenous levels of extracellular signal-regulated kinase (ERK) 1/2. Furthermore, both in the presence and absence of SiO2 particles, the addition of EGF increased cell migration. EGF also stimulated cellular uptake of 130 nm SiO2 particles but not 1 μm particles. The increased uptake is primarily associated with EGF-stimulated macropinocytosis.Conclusion: This study shows that SiO2 particle uptake interferes with cellular signaling pathways and can be boosted by concurrent exposure to the bioactive molecule EGF. SiO2 particles, both alone and in combination with the ligand EGF, interfere with EGFR signaling pathway in a size-dependent manner.Keywords: endocytosis, nanoparticles, epidermal growth factor, cellular signalinghttps://www.dovepress.com/cellular-uptake-of-silica-particles-influences-egfr-signaling-pathway--peer-reviewed-fulltext-article-IJNendocytosisnanoparticlesepidermal growth factorcellular signaling. |
| spellingShingle | Sousa de Almeida M Roshanfekr A Balog S Petri-Fink A Rothen-Rutishauser B Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF International Journal of Nanomedicine endocytosis nanoparticles epidermal growth factor cellular signaling. |
| title | Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF |
| title_full | Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF |
| title_fullStr | Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF |
| title_full_unstemmed | Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF |
| title_short | Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF |
| title_sort | cellular uptake of silica particles influences egfr signaling pathway and is affected in response to egf |
| topic | endocytosis nanoparticles epidermal growth factor cellular signaling. |
| url | https://www.dovepress.com/cellular-uptake-of-silica-particles-influences-egfr-signaling-pathway--peer-reviewed-fulltext-article-IJN |
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