Trk Inhibition Reduces Tumorsphere Formation and Changes Expression of Stemness Markers in SK-ES-1 Ewing Sarcoma Cells

Authors

  • Rafael Pereira dos Santos Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre (HCPA), Centro de Pesquisa Experimental, Laboratório de Câncer e Neurobiologia; Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia. Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-0949-9648
  • Bruna Almeida dos Santos Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre (HCPA), Centro de Pesquisa Experimental, Laboratório de Câncer e Neurobiologia; Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia. Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-3256-5500
  • Lauro Gregianin Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre (HCPA), Escola de Medicina, Departamento de Pediatria; Serviço de Oncologia Pediátrica. Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-0788-7858
  • André Tessainer Brunetto Instituto do Câncer Infantil. Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-7958-1279
  • Algemir Lunardi Brunetto Instituto do Câncer Infantil. Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-0668-6894
  • Rafael Roesler Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre (HCPA), Centro de Pesquisa Experimental, Laboratório de Câncer e Neurobiologia; Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia. Porto Alegre (RS), Brazil. https://orcid.org/0000-0001-6016-2261
  • Caroline Brunetto de Farias Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre (HCPA), Centro de Pesquisa Experimental, Laboratório de Câncer e Neurobiologia; Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia. Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-6435-6626

DOI:

https://doi.org/10.32635/2176-9745.RBC.2023v69n4.4262

Keywords:

Receptor, trkA, receptors, nerve growth factor, neoplastic stem cells, sarcoma, Ewing

Abstract

Introduction: Ewing sarcoma (ES) is a highly aggressive type of childhood cancer characterized by a chromosomal translocation resulting in fusions between the gene encoding EWS RNA Binding Protein 1 (EWSR1) and one gene of the ETS family, most frequently FLI-1, resulting in the EWS-FLI1 aberrant transcription factor. ES tumors can contain a subpopulation of cells showing cancer stem cell (CSC) features, which express stemness markers including CD133, OCT4 (Octamer-binding transcription factor 4), and NANOG, and display capacity to form tumorspheres likely enriched in CSCs. Neurotrophin (NT) receptors of the tropomyosin receptor kinase (Trk) family (TrkA, TrkB, and TrkC) may play a role in stimulating ES progression, but their possible role in CSCs remains unknown. Objective: To verify the effect of Trks inhibition on the formation of tumorspheres as well as the gene expression of stem markers. Method: The cells were dissociated and the formation of spheres was induced with supplemented culture medium and the K252a treatment was performed. After RNA extraction, mRNA expression levels of target genes Prom1 (CD133), OCT4 (POU5F1), SOX2, and Musashi-1 (MSI1) were analyzed by qPCR. Results: The pan-Trk inhibitor K252a (100 or 500 mM) hindered tumorsphere formation in human SK-ES-1 ES cell cultures. K252a also reduced mRNA expression of Prom1 (CD133-coding gene) while enhancing expression of OCT4. No changes in mRNA levels of SOX2 or Musashi-1 were observed. Conclusion: These findings provide the first evidence suggesting that Trk activity can influence stemness in ES cells.

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References

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Published

2024-01-05

How to Cite

1.
Pereira dos Santos R, Almeida dos Santos B, Gregianin L, Tessainer Brunetto A, Lunardi Brunetto A, Roesler R, Brunetto de Farias C. Trk Inhibition Reduces Tumorsphere Formation and Changes Expression of Stemness Markers in SK-ES-1 Ewing Sarcoma Cells. Rev. Bras. Cancerol. [Internet]. 2024 Jan. 5 [cited 2025 Apr. 15];69(4):e-174262. Available from: https://rbc.inca.gov.br/index.php/revista/article/view/4262

Issue

Vol. 69 No. 4 (2023): oct./nov./dec.

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ORIGINAL ARTICLE

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