2. Academic Validation
  3. Inhibition of the platelet-derived growth factor receptor beta (PDGFRB) using gene silencing, crenolanib besylate, or imatinib mesylate hampers the malignant phenotype of mesothelioma cell lines

Inhibition of the platelet-derived growth factor receptor beta (PDGFRB) using gene silencing, crenolanib besylate, or imatinib mesylate hampers the malignant phenotype of mesothelioma cell lines

  • Genes Cancer. 2017 Jan;8(1-2):438-452. doi: 10.18632/genesandcancer.129.
Ombretta Melaiu 1 2,  Calogerina Catalano 3,  Chiara De Santi 4,  Monica Cipollini 2,  Gisella Figlioli 5,  Lucia Pellè 2,  Elisa Barone 2,  Monica Evangelista 6,  Alice Guazzelli 7,  Laura Boldrini 8,  Elisa Sensi 8,  Alessandra Bonotti 9,  Rudy Foddis 10,  Alfonso Cristaudo 10,  Luciano Mutti 7,  Gabriella Fontanini 8,  Federica Gemignani 2,  Stefano Landi 2
Affiliations

Affiliations

  • 1 Paediatric Haematology/Oncology Department, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
  • 2 Department of Biology, University of Pisa, Pisa, Italy.
  • 3 Division of molecular genetic epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 4 Department of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
  • 5 IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy.
  • 6 Institute of Clinical Physiology (IFC), CNR, Pisa, Italy.
  • 7 School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom.
  • 8 Department of Surgical, Medical, Molecular Pathology and Critical Care, Division of Pathological Anatomy, University of Pisa, Pisa, Italy.
  • 9 Preventive and Occupational Medicine, University Hospital of Pisa, Pisa, Italy.
  • 10 Department of Translational Research and of new Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
PMID: 28435517 DOI: 10.18632/genesandcancer.129
Abstract

Malignant pleural mesothelioma (MPM) is a Cancer of the pleural cavity resistant to chemotherapy. The identification of novel therapeutic targets is needed to improve its poor prognosis. Following a review of literature and a screening of specimens we found that platelet-derived growth factor receptor beta (PDGFRB) is over-expressed, but not somatically mutated, in MPM tissues. We aimed to ascertain whether PDGFRB is a MPM-cancer driver gene. The approaches employed included the use of gene silencing and the administration of small molecules, such as crenolanib and imatinib (PDGFR inhibitors) on MPM cell lines (IstMes2, Mero-14, Mero-25). Met5A cells were used as non-malignant mesothelial cell line. PDGFRB-silencing caused a decrease in the proliferation rate, and a reduced colony formation capacity, as well as an increase of the share of cells in sub-G1 and in G2 phase, and increased apoptotic rate of MPM cell lines. Loss of migration ability was also observed. Similar, or even further enhanced, results were obtained with crenolanib. Imatinib showed the least effective activity on the phenotype. In conclusion, our study highlights PDGFRB as target with a clear role in MPM tumorigenesis and provided a rationale to explore further the efficacy of crenolanib in MPM patients, with promising results.

Keywords

Malignant Pleural Mesothelioma; PDGFRB; RNA interference; drug inhibitors; therapeutic targets.

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