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CD44 Modulates Cell Migration and Invasion in Ewing Sarcoma Cells.

Enrique Fernández-Tabanera1,2,3, Laura García-García1, Carlos Rodríguez-Martín1,2

  • 1Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.

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|July 29, 2023
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Summary

CD44 standard isoform (CD44s) is overexpressed in migratory Ewing sarcoma cells. CD44s reduces proliferation but enhances migration and invasion, regulated by EWSR1::FLI1 levels.

Keywords:
CD44EWSR1::FLI1Ewing sarcomacell invasivenesscell migration

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Ewing sarcoma is driven by the EWSR1::FLI1 oncogenic transcription factor.
  • EWSR1::FLI1 levels can vary, creating distinct cell populations with different behaviors.
  • EWSR1::FLI1low cells exhibit migratory and invasive properties, while EWSR1::FLI1high cells are more proliferative.

Purpose of the Study:

  • To investigate the role of the CD44 standard isoform (CD44s) in Ewing sarcoma.
  • To characterize the functional impact of CD44s on cell proliferation, migration, and invasion.
  • To understand the relationship between CD44s expression and EWSR1::FLI1 levels.

Main Methods:

  • Utilized three doxycycline-inducible Ewing sarcoma cell models (A673, MHH-ES1, CADO-ES1).
  • Assessed proliferation, clonogenicity, migration, and invasion abilities following CD44s modulation.
  • Investigated the effect of different molecular weights of hyaluronic acid (HA) on cell migration.
  • Analyzed CD44s expression in relation to EWSR1::FLI1 knockdown.

Main Results:

  • CD44s overexpression reduced proliferation across all tested cell lines but did not affect clonogenicity.
  • CD44s enhanced cell migration in A673 and MHH-ES1 cell lines, with varying effects of hyaluronic acid (HMW-HA blocked, LMW-HA increased).
  • Invasion ability correlated with CD44s expression in specific cell lines (A673, MHH-ES1).
  • CD44s was found to be upregulated upon EWSR1::FLI1 knockdown.

Conclusions:

  • CD44s is a key regulator of migratory and invasive phenotypes in EWSR1::FLI1low Ewing sarcoma cells.
  • CD44s influences cell proliferation and migration, with its effects potentially modulated by the tumor microenvironment (e.g., hyaluronic acid).
  • The interplay between EWSR1::FLI1 and CD44s highlights a potential therapeutic target for managing Ewing sarcoma cell dissemination.