CD44 Modulates Cell Migration and Invasion in Ewing Sarcoma Cells
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Published:2023-07-21
Issue:14
Volume:24
Page:11774
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Fernández-Tabanera Enrique123ORCID, García-García Laura1, Rodríguez-Martín Carlos12ORCID, Cervera Saint T.12ORCID, González-González Laura1ORCID, Robledo Cristina1, Josa Santiago1, Martínez Selene1, Chapado Luis4, Monzón Sara4, Melero-Fernández de Mera Raquel M.12ORCID, Alonso Javier12ORCID
Affiliation:
1. Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain 2. Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III (U758, CB06/07/1009, CIBERER-ISCIII), 28029 Madrid, Spain 3. Universidad Nacional de Educación a Distancia (UNED), 28015 Madrid, Spain 4. Bioinformatics Unit, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain
Abstract
The chimeric EWSR1::FLI1 transcription factor is the main oncogenic event in Ewing sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels can fluctuate in Ewing sarcoma cells, giving rise to two cell populations. EWSR1::FLI1low cells present a migratory and invasive phenotype, while EWSR1::FLI1high cells are more proliferative. In this work, we described how the CD44 standard isoform (CD44s), a transmembrane protein involved in cell adhesion and migration, is overexpressed in the EWSR1::FLI1low phenotype. The functional characterization of CD44s (proliferation, clonogenicity, migration, and invasion ability) was performed in three doxycycline-inducible Ewing sarcoma cell models (A673, MHH-ES1, and CADO-ES1). As a result, CD44s expression reduced cell proliferation in all the cell lines tested without affecting clonogenicity. Additionally, CD44s increased cell migration in A673 and MHH-ES1, without effects in CADO-ES1. As hyaluronan is the main ligand of CD44s, its effect on migration ability was also assessed, showing that high molecular weight hyaluronic acid (HMW-HA) blocked cell migration while low molecular weight hyaluronic acid (LMW-HA) increased it. Invasion ability was correlated with CD44 expression in A673 and MHH-ES1 cell lines. CD44s, upregulated upon EWSR1::FLI1 knockdown, regulates cell migration and invasion in Ewing sarcoma cells.
Funder
Instituto de Salud Carlos III Asociación Pablo Ugarte Asociación Candela Riera ASION a CIBERER contract
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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