Role of Extracellular Vimentin in Cancer-Cell Functionality and Its Influence on Cell Monolayer Permeability Changes Induced by SARS-CoV-2 Receptor Binding Domain
| Autor: | Philipp Jung, Markus Bischoff, Franziska Lautenschläger, Divyendu Goud Thalla |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
SARS-CoV-2 receptor binding domain Cell Membrane Permeability Cell Vimentin 0302 clinical medicine Breast Biology (General) Receptor Cytoskeleton skin and connective tissue diseases extracellular vimentin IGF-1 receptor cancer Cells Cultured Spectroscopy biology Chemistry Cell migration General Medicine Extracellular Matrix Computer Science Applications Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus Female QH301-705.5 Protein domain Breast Neoplasms Article Catalysis Inorganic Chemistry 03 medical and health sciences Protein Domains Extracellular medicine Humans Physical and Theoretical Chemistry QD1-999 Molecular Biology Organic Chemistry 030104 developmental biology Cancer cell biology.protein |
| Zdroj: | International Journal of Molecular Sciences; Volume 22; Issue 14; Pages: 7469 International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 7469, p 7469 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22147469 |
| Popis: | The cytoskeletal protein vimentin is secreted under various physiological conditions. Extracellular vimentin exists primarily in two forms: attached to the outer cell surface and secreted into the extracellular space. While surface vimentin is involved in processes such as viral infections and cancer progression, secreted vimentin modulates inflammation through reduction of neutrophil infiltration, promotes bacterial elimination in activated macrophages, and supports axonal growth in astrocytes through activation of the IGF-1 receptor. This receptor is overexpressed in cancer cells, and its activation pathway has significant roles in general cellular functions. In this study, we investigated the functional role of extracellular vimentin in non-tumorigenic (MCF-10a) and cancer (MCF-7) cells through the evaluation of its effects on cell migration, proliferation, adhesion, and monolayer permeability. Upon treatment with extracellular recombinant vimentin, MCF-7 cells showed increased migration, proliferation, and adhesion, compared to MCF-10a cells. Further, MCF-7 monolayers showed reduced permeability, compared to MCF-10a monolayers. It has been shown that the receptor binding domain of SARS-CoV-2 spike protein can alter blood–brain barrier integrity. Surface vimentin also acts as a co-receptor between the SARS-CoV-2 spike protein and the cell-surface angiotensin-converting enzyme 2 receptor. Therefore, we also investigated the permeability of MCF-10a and MCF-7 monolayers upon treatment with extracellular recombinant vimentin, and its modulation of the SARS-CoV-2 receptor binding domain. These findings show that binding of extracellular recombinant vimentin to the cell surface enhances the permeability of both MCF-10a and MCF-7 monolayers. However, with SARS-CoV-2 receptor binding domain addition, this effect is lost with MCF-7 monolayers, as the extracellular vimentin binds directly to the viral domain. This defines an influence of extracellular vimentin in SARS-CoV-2 infections. |
| Databáze: | OpenAIRE |
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