Primary culture of undifferentiated pleomorphic sarcoma: Molecular characterization and response to anticancer agents

Alessandro De Vita, Federica Recine, Laura Mercatali, Giacomo Miserocchi, Chiara Spadazzi, Chiara Liverani, Alberto Bongiovanni, Federica Pieri, Roberto Casadei, Nada Riva, Valentina Fausti, Dino Amadori, Toni Ibrahim

Research output: Contribution to journalArticle

Abstract

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm with no specific line of differentiation. Eribulin, a novel synthetic microtubule inhibitor, has shown anticancer activity in several tumors, including soft tissue sarcomas (STS). We investigated the molecular biology of UPS, and the mechanisms of action of this innovative microtubule-depolymerizing drug. A primary culture from a patient with UPS was established and characterized in terms of gene expression. The activity of eribulin was also compared with that of other drugs currently used for STS treatment, including trabectedin. Finally, Western blot analysis was performed to better elucidate the activity of eribulin. Our results showed an upregulation of epithelial mesenchymal transition-related genes, and a downregulation of epithelial markers. Furthermore, genes involved in chemoresistance were upregulated. Pharmacological analysis confirmed limited sensitivity to chemotherapy. Interestingly, eribulin exhibited a similar activity to that of standard treatments. Molecular analysis revealed the expression of cell cycle arrest-related and pro-apoptotic-related proteins. These findings are suggestive of aggressive behavior in UPS. Furthermore, the identification of chemoresistance-related genes could facilitate the development of innovative drugs to improve patient outcome. Overall, the results from the present study furnish a rationale for elucidating the role of eribulin for the treatment of UPS.

Original languageEnglish
Article number2662
JournalInternational Journal of Molecular Sciences
Volume18
Issue number12
DOIs
Publication statusPublished - Dec 8 2017

Keywords

  • Chemotherapy
  • Drug resistance
  • EMT
  • Eribulin
  • Malignant fibrous histiocytoma
  • Primary culture
  • Undifferentiated pleomorphic sarcoma

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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