The expression level of VEGFR2 regulates mechanotransduction, tumor growth and metastasis of high grade serous ovarian cancer cells.

Autor: Grillo E; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy; The Mechanobiology research center, University of Brescia, Brescia, Italy. Electronic address: elisabetta.grillo@unibs.it., Ravelli C; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy; The Mechanobiology research center, University of Brescia, Brescia, Italy., Corsini M; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy; The Mechanobiology research center, University of Brescia, Brescia, Italy., Domenichini M; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy., Scamozzi M; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy., Zizioli D; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy; The Mechanobiology research center, University of Brescia, Brescia, Italy., Capoferri D; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy., Bresciani R; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy; The Mechanobiology research center, University of Brescia, Brescia, Italy; Highly Specialized Laboratory, ASST Spedali Civili di Brescia, Piazzale Spedali Civili 1, Brescia 25123, Italy., Romani C; Angelo Nocivelli Institute of Molecular Medicine, ASST Spedali Civili of Brescia, Brescia, Italy; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy., Mitola S; Department of Molecular and Translational Medicine, University of Brescia, Via Branze 39, Brescia 25123, Italy; The Mechanobiology research center, University of Brescia, Brescia, Italy. Electronic address: stefania.mitola@unibs.it.
Jazyk: angličtina
Zdroj: European journal of cell biology [Eur J Cell Biol] 2024 Dec; Vol. 103 (4), pp. 151459. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1016/j.ejcb.2024.151459
Abstrakt: Recent data shows that alterations in the expression and/or activation of the vascular endothelial growth factor receptor 2 (VEGFR2) in high grade serous ovarian cancer (HGSOC) modulate tumor progression. However, controversial results have been obtained, showing that in some cases VEGFR2 inhibition can promote tumorigenesis and metastasis. Thus, it is urgent to better define the role of the VEGF/VEGFR2 system to understand/predict the effects of its inhibitors administered as anti-angiogenic in HGSOC. Here, we modulated the expression levels of VEGFR2 and analyzed the effects in two cellular models of HGSOC. VEGFR2 silencing (or its pharmacological inhibition) promote the growth and invasive potential of OVCAR3 cells in vitro and in vivo. Consistent with this, the low levels of VEGFR2 in OV7 cells are associated with more pronounced proliferative and motile phenotypes when compared to OVCAR3 cells, and VEGFR2 overexpression in OV7 cells inhibits cell growth. In vitro data confirmed that VEGFR2 silencing in OVCAR3 cells favors the acquisition of an invasive phenotype by loosening cell-ECM contacts, reducing the size and the signaling of focal adhesion contacts (FAs). This is translated into a reduced FAK activity at FAs, ECM-dependent alterations of mechanical forces through FAs and YAP nuclear translocation. Together, the data show that low expression, silencing or inhibition of VEGFR2 in HGSOC cells alter mechanotransduction and lead to the acquisition of a pro-proliferative/invasive phenotype which explains the need for a more cautious use of anti-VEGFR2 drugs in ovarian cancer.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier GmbH.)
Databáze: MEDLINE
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