Your browser doesn't support javascript.
loading
Identification of a set of genes potentially responsible for resistance to ferroptosis in lung adenocarcinoma cancer stem cells.
Ascenzi, Francesca; Esposito, Antonella; Bruschini, Sara; Salvati, Valentina; De Vitis, Claudia; De Arcangelis, Valeria; Ricci, Giulia; Catizione, Angiolina; di Martino, Simona; Buglioni, Simonetta; Bassi, Massimiliano; Venuta, Federico; De Nicola, Francesca; Massacci, Alice; Grassucci, Isabella; Pallocca, Matteo; Ricci, Alberto; Fanciulli, Maurizio; Ciliberto, Gennaro; Mancini, Rita.
Afiliação
  • Ascenzi F; Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Esposito A; Department of Clinical and Molecular Medicine, Sant' Andrea Hospital-Sapienza University of Rome, Rome, Italy.
  • Bruschini S; Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy.
  • Salvati V; Experimental Pharmacology Unit, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy.
  • De Vitis C; Department of Clinical and Molecular Medicine, Sant' Andrea Hospital-Sapienza University of Rome, Rome, Italy.
  • De Arcangelis V; SAFU Laboratory, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Ricci G; Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Catizione A; Department of Clinical and Molecular Medicine, Sant' Andrea Hospital-Sapienza University of Rome, Rome, Italy.
  • di Martino S; Department of Clinical and Molecular Medicine, Sant' Andrea Hospital-Sapienza University of Rome, Rome, Italy.
  • Buglioni S; Department of Experimental Medicine, Università Degli Studi Della Campania Luigi Vanvitelli, Naples, Italy.
  • Bassi M; Department of Anatomy, Histology, Forensic-Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.
  • Venuta F; Pathology Unit, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
  • De Nicola F; Pathology Unit, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
  • Massacci A; Thoracic Surgery Unit, Sapienza University of Rome, Rome, Italy.
  • Grassucci I; Thoracic Surgery Unit, Sapienza University of Rome, Rome, Italy.
  • Pallocca M; SAFU Laboratory, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Ricci A; Biostatistics, Bioinformatics and Clinical Trial Center, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Fanciulli M; Biostatistics, Bioinformatics and Clinical Trial Center, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  • Ciliberto G; Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy.
  • Mancini R; Respiratory Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
Cell Death Dis ; 15(4): 303, 2024 Apr 29.
Article em En | MEDLINE | ID: mdl-38684666
ABSTRACT
Scientific literature supports the evidence that cancer stem cells (CSCs) retain inside low reactive oxygen species (ROS) levels and are, therefore, less susceptible to cell death, including ferroptosis, a type of cell death dependent on iron-driven lipid peroxidation. A collection of lung adenocarcinoma (LUAD) primary cell lines derived from malignant pleural effusions (MPEs) of patients was used to obtain 3D spheroids enriched for stem-like properties. We observed that the ferroptosis inducer RSL3 triggered lipid peroxidation and cell death in LUAD cells when grown in 2D conditions; however, when grown in 3D conditions, all cell lines underwent a phenotypic switch, exhibiting substantial resistance to RSL3 and, therefore, protection against ferroptotic cell death. Interestingly, this phenomenon was reversed by disrupting 3D cells and growing them back in adherence, supporting the idea of CSCs plasticity, which holds that cancer cells have the dynamic ability to transition between a CSC state and a non-CSC state. Molecular analyses showed that ferroptosis resistance in 3D spheroids correlated with an increased expression of antioxidant genes and high levels of proteins involved in iron storage and export, indicating protection against oxidative stress and low availability of iron for the initiation of ferroptosis. Moreover, transcriptomic analyses highlighted a novel subset of genes commonly modulated in 3D spheroids and potentially capable of driving ferroptosis protection in LUAD-CSCs, thus allowing to better understand the mechanisms of CSC-mediated drug resistance in tumors.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Adenocarcinoma de Pulmão / Ferroptose / Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Adenocarcinoma de Pulmão / Ferroptose / Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article