EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells

Schelch, Karin; Vogel, Lisa; Schneller, Anja; Brankovic, Jelena; Mohr, Thomas; Mayer, Rupert L.; Slany, Astrid; Gerner, Christopher; Grusch, Michael

doi:10.3389/fcell.2021.634371

Cited by 19 publications

(10 citation statements)

References 63 publications

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“…Epidermal growth factor is known to influence not only cell proliferation, but also cell migration and invasion. 39 To investigate the effect of EGF and SiO 2 particles on cell migration, a cell migration assay was performed for 24 h ( Figure 5D and E ). After 6 hours, an increase in cell migration in the presence of EGF and EGF with 1 µm particles is shown.…”

Section: Resultsmentioning

confidence: 99%

Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF

Almeida¹,

Roshanfekr²,

Balog³

et al. 2023

IJN

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Background 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 (SiO 2 ) 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 SiO 2 particles with core diameters of 130 nm and 1 µm without affecting cell proliferation or migration. However, both SiO 2 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 SiO 2 particles, the addition of EGF increased cell migration. EGF also stimulated cellular uptake of 130 nm SiO 2 particles but not 1 µm particles. The increased uptake is primarily associated with EGF-stimulated macropinocytosis. Conclusion This study shows that SiO 2 particle uptake interferes with cellular signaling pathways and can be boosted by concurrent exposure to the bioactive molecule EGF. SiO 2 particles, both alone and in combination with the ligand EGF, interfere with EGFR signaling pathway in a size-dependent manner.

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Section: Resultsmentioning

confidence: 99%

Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF

Almeida¹,

Roshanfekr²,

Balog³

et al. 2023

IJN

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“…EVP‐induced EMT program may also result in increased cell migration, although the two processes can be independent of one another (He et al , 2019c; Schelch et al , 2021). Direct autocrine and paracrine shuttling of EVP cargo, including tetraspanins, promotes in vitro migration of cancer cells (Pace et al , 2019; Matsumoto et al , 2020; Huang et al , 2020c).…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles and particles impact the systemic landscape of cancer

et al. 2022

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Intercellular cross talk between cancer cells and stromal and immune cells is essential for tumor progression and metastasis. Extracellular vesicles and particles (EVPs) are a heterogeneous class of secreted messengers that carry bioactive molecules and that have been shown to be crucial for this cell-cell communication. Here, we highlight the multifaceted roles of EVPs in cancer. Functionally, transfer of EVP cargo between cells influences tumor cell growth and invasion, alters immune cell composition and function, and contributes to stromal cell activation. These EVP-mediated changes impact local tumor progression, foster cultivation of pre-metastatic niches at distant organspecific sites, and mediate systemic effects of cancer. Furthermore, we discuss how exploiting the highly selective enrichment of molecules within EVPs has profound implications for advancing diagnostic and prognostic biomarker development and for improving therapy delivery in cancer patients. Altogether, these investigations into the role of EVPs in cancer have led to discoveries that hold great promise for improving cancer patient care and outcome.

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“…Induction of apoptosis by exosomal content is also reported [14] but in our case, the exosome cannot induce apoptosis in PC3 cells. Genetic data reveals that PC3 cells have deleted PTEN where lung cancer cell A549 has mutated Ras protein [14,19]. This prompted us to look for PTEN in the A549 derived exosomes.…”

Section: Discussionmentioning

confidence: 99%

DNA damage induced cellular senescence and it’s PTEN-armed exosomes—the warriors against prostate carcinoma cells

et al. 2022

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Exosomes are one type of small extracellular vesicles having a size range of 30-150 nm and secreted by the endosomal compartment of most eukaryotic cells. It has been found that exosomes can serve as a communicating vehicle to transfer information among cells and thus can be associated with numerous physiological and pathological functions. In this study, we have isolated exosomes from two different human cancer cell lines. Isolated exosomes were characterized by scanning electron microscopy, DLS and by western blotting. It was observed that exosomes isolated from mock treated human lung epithelial carcinoma (A549) cells or Hela cells exerted growth arrest to the human prostate carcinoma (PC3) cells, but no growth arrest was observed in case of normal human lung broblast cell line (WI38). Additionally, exosomes isolated from PC3 cells have no effect on PC3 cells. This is also true for exosomes isolated from H 2 O 2 induced senescent human lung cancer cells (A549). Analysis of exosome content by western blotting reveals the presence of PTEN in the exosome of lung cancer cells. Functional analysis of PTEN pathways in PC3 cells indicates the inactivation of Akt in exosome treated cells. Therefore, from our study we have concluded that exosomes secreted from A549 cells which contain functional PTEN, may be used for delivery of PTEN to cancer cells without functional PTEN.

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EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells

Cited by 19 publications

References 63 publications

Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF

Cellular Uptake of Silica Particles Influences EGFR Signaling Pathway and is Affected in Response to EGF

Extracellular vesicles and particles impact the systemic landscape of cancer

DNA damage induced cellular senescence and it’s PTEN-armed exosomes—the warriors against prostate carcinoma cells

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