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ISG15 as a prognostic biomarker in solitary fibrous tumour.
Mondaza-Hernandez, Jose L; Moura, David S; Lopez-Alvarez, María; Sanchez-Bustos, Paloma; Blanco-Alcaina, Elena; Castilla-Ramirez, Carolina; Collini, Paola; Merino-Garcia, Jose; Zamora, Jorge; Carrillo-Garcia, Jaime; Maestro, Roberta; Hindi, Nadia; Garcia-Foncillas, Jesus; Martin-Broto, Javier.
Afiliação
  • Mondaza-Hernandez JL; Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS/FJD-UAM), Madrid, Spain.
  • Moura DS; University Hospital General de Villalba, Madrid, Spain.
  • Lopez-Alvarez M; Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS/FJD-UAM), Madrid, Spain.
  • Sanchez-Bustos P; University Hospital General de Villalba, Madrid, Spain.
  • Blanco-Alcaina E; Institute of Biomedicine of Sevilla (IBIS, HUVR, CSIC Universidad de Sevilla), Seville, Spain.
  • Castilla-Ramirez C; Institute of Biomedicine of Sevilla (IBIS, HUVR, CSIC Universidad de Sevilla), Seville, Spain.
  • Collini P; Institute of Biomedicine of Sevilla (IBIS, HUVR, CSIC Universidad de Sevilla), Seville, Spain.
  • Merino-Garcia J; CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
  • Zamora J; Pathology Department, University Hospital Virgen del Rocio, Seville, Spain.
  • Carrillo-Garcia J; Soft Tissue and Bone Pathology, Histopathology and Pediatric Pathology Unit, Diagnostic Pathology and Laboratory Medicine Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Instituto Nazionale Tumori, Milan, Italy.
  • Maestro R; Pathology Department, University Hospital Fundacion Jimenez Diaz, Universidad Autonoma, Av. Reyes Catolicos 2, 28040, Madrid, Spain.
  • Hindi N; Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS/FJD-UAM), Madrid, Spain.
  • Garcia-Foncillas J; University Hospital General de Villalba, Madrid, Spain.
  • Martin-Broto J; Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS/FJD-UAM), Madrid, Spain.
Cell Mol Life Sci ; 79(8): 434, 2022 Jul 21.
Article em En | MEDLINE | ID: mdl-35864381
BACKGROUND: Solitary fibrous tumour (SFT) is a rare mesenchymal malignancy that lacks robust prognostic and predictive biomarkers. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier, associated with tumour progression, and with poor survival of SFT patients, as previous published by our group. Here, we describe the role of ISG15 in the biology of this rare tumour. METHODS: ISG15 expression was assessed by immunohistochemistry in tissue microarrays from SFT patients and tested for correlation with progression-free survival and overall survival (OS). The effects of ISG15 knockdown or induction were investigated for cancer stem cell (CSC) characteristics and for drug sensitivity in unique in vitro models of SFT. RESULTS: The prognostic value of ISG15 for OS was validated at protein level in malignant SFT patients, prospectively treated with pazopanib and enrolled in GEIS-32 trial. In SFT in vitro models, ISG15 knockdown lead to a decrease in the expression of CSC-related genes, including SOX2, NANOG, ALDH1A1, ABCB1 and ABCC1. Likewise, ISG15 downregulation decreased the clonogenic/ tumoursphere-forming ability of SFT cells, while enhancing apoptotic cell death after doxorubicin, pazopanib or trabectedin treatment in 3D cell cultures. The regulation of CSC-related genes by ISG15 was confirmed after inducing its expression with interferon-ß1; ISG15 induction upregulated 1.28- to 451-fold the expression of CSC-associated genes. CONCLUSIONS: ISG15 is a prognostic factor in malignant SFT, regulating the expression of CSC-related genes and CSCs maintenance. Our results suggest that ISG15 could be a novel therapeutic target in SFT, which could improve the efficacy of the currently available treatments.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interferons / Tumores Fibrosos Solitários Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interferons / Tumores Fibrosos Solitários Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article