Osteopontin-4 (OPN-4) Suppresses Tumor Progression Features Whilst Sensitizing c643 Anaplastic Thyroid Cells to

Gabriela Ribeiro Silva1,2, Amanda Lewis Rubim2, Flavia da Cunha Vasconcelos2,3

  • 1Programa de Pós-Graduação em Ciências Biomédicas, Fisiologia e Farmacologia, Instituto Biomédico, Niterói CEP 24210-130, Brazil.

Biomedicines
|May 27, 2026
PubMed

Insights

Osteopontin-4 (OPN-4) overexpression in anaplastic thyroid carcinoma (ATC) cells reduced proliferation and migration. OPN-4 may serve as a biomarker for therapeutic response in personalized ATC treatment strategies.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Anaplastic thyroid carcinoma (ATC) is a highly aggressive endocrine malignancy.
  • Osteopontin (OPN) is aberrantly expressed in ATC.
  • The functional roles of OPN splicing isoforms, specifically OPN-4, in ATC remain largely unknown.

Purpose of the Study:

  • To elucidate the functional roles of OPN-4 in anaplastic thyroid carcinoma cells.
  • To investigate the impact of OPN-4 overexpression on ATC cell behavior and response to therapy.

Main Methods:

  • Ectopic overexpression of OPN-4 in the c643 ATC cell line.
  • In vitro functional assays including proliferation, viability, migration, clonogenicity, cell cycle, and apoptosis.
  • Assessment in 2D monolayers and 3D spheroids within a microfluidic system.
  • Evaluation of combined OPN-4 overexpression and sorafenib treatment.

Main Results:

  • OPN-4 overexpression significantly reduced ATC cell proliferation, viability, migration, and clonogenicity.
  • OPN-4 overexpression caused G0/G1 cell cycle arrest without affecting apoptosis or other OPN splicing isoforms.
  • No significant differences in spheroid size or viability were observed in 3D models.
  • OPN-4 enhanced sorafenib efficacy in cell viability under dynamic perfusion conditions.

Conclusions:

  • OPN-4 overexpression appears to inhibit certain aspects of tumor progression in ATC cells.
  • OPN-4 warrants further investigation as a potential biomarker for predicting therapeutic response in personalized ATC treatment strategies.

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