Please use this identifier to cite or link to this item: doi:10.22028/D291-34460
Title: Role of Extracellular Vimentin in Cancer-Cell Functionality and Its Influence on Cell Monolayer Permeability Changes Induced by SARS-CoV-2 Receptor Binding Domain
Author(s): Thalla, Divyendu Goud
Jung, Philipp
Bischoff, Markus
Lautenschläger, Franziska
Language: English
Title: International Journal of Molecular Sciences
Volume: 22
Issue: 14
Publisher/Platform: MDPI
Year of Publication: 2021
Free key words: extracellular vimentin
IGF-1 receptor
SARS-CoV-2 receptor binding domain
DDC notations: 500 Science
610 Medicine and health
Publikation type: Journal Article
Abstract: 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.
DOI of the first publication: 10.3390/ijms22147469
Link to this record: urn:nbn:de:bsz:291--ds-344606
ISSN: 1422-0067
Date of registration: 3-Aug-2021
Faculty: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Department: M - Infektionsmedizin
NT - Physik
Professorship: M - Prof. Dr. Dr. Sören Becker
NT - Jun.-Prof. Dr. Franziska Lautenschläger
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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