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Int. J. Mol. Sci. 2017, 18(12), 2662; https://doi.org/10.3390/ijms18122662

Primary Culture of Undifferentiated Pleomorphic Sarcoma: Molecular Characterization and Response to Anticancer Agents

1
Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via P. Maroncelli 40, 47014 Meldola, Italy
2
Pathology Unit, Morgagni-Pierantoni Hospital, Via Carlo Forlanini 34, 47121 Forlì, Italy
3
Department of Orthopedics, Istituto Ortopedico Rizzoli, University of Bologna, Via Pupilli 1, 40136 Bologna, Italy
*
Author to whom correspondence should be addressed.
Received: 19 October 2017 / Revised: 23 November 2017 / Accepted: 6 December 2017 / Published: 8 December 2017
(This article belongs to the Special Issue Current Advances in Soft Tissue and Bone Sarcoma)
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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. View Full-Text
Keywords: undifferentiated pleomorphic sarcoma; malignant fibrous histiocytoma; primary culture; EMT; drug resistance; chemotherapy; eribulin undifferentiated pleomorphic sarcoma; malignant fibrous histiocytoma; primary culture; EMT; drug resistance; chemotherapy; eribulin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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De Vita, A.; Recine, F.; Mercatali, L.; Miserocchi, G.; Spadazzi, C.; Liverani, C.; Bongiovanni, A.; Pieri, F.; Casadei, R.; Riva, N.; Fausti, V.; Amadori, D.; Ibrahim, T. Primary Culture of Undifferentiated Pleomorphic Sarcoma: Molecular Characterization and Response to Anticancer Agents. Int. J. Mol. Sci. 2017, 18, 2662.

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