> Details

Magnaghi, Paola; Bosotti, Roberta; Amboldi, Nadia; Cozzi, Liviana; Somaschini, Alessio; Stacchiotti, Silvia; Bozzi, Fabio; Tamborini, Elena; Conca, Elena; Pilotti, Silvana; Pierotti, Marco A.; Di Bella, Sebastiano; Cusi, Carlo; Ballinari, Dario; Galvani, Arturo; Salom, Barbara; Isacchi, Antonella

Abstract 74: Establishment and characterization of the new sacral chordoma cell line Chor-IN-1

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Abstract 74: Establishment and characterization of the new sacral chordoma cell line Chor-IN-1
  • Contributor: Magnaghi, Paola; Bosotti, Roberta; Amboldi, Nadia; Cozzi, Liviana; Somaschini, Alessio; Stacchiotti, Silvia; Bozzi, Fabio; Tamborini, Elena; Conca, Elena; Pilotti, Silvana; Pierotti, Marco A.; Di Bella, Sebastiano; Cusi, Carlo; Ballinari, Dario; Galvani, Arturo; Salom, Barbara; Isacchi, Antonella
  • imprint: American Association for Cancer Research (AACR), 2015
  • Published in: Cancer Research
  • Language: English
  • DOI: 10.1158/1538-7445.am2015-74
  • ISSN: 1538-7445; 0008-5472
  • Keywords: Cancer Research ; Oncology
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:p>Chordomas are rare, slowly growing but locally invasive bone tumors, derived from notocord remnants and characterized by the expression of “Brachyury” transcription factor.</jats:p> <jats:p>No standard medical therapy is available for this indication that is resistant to chemotherapy. Surgery associated to radiation, is the conventional treatment, but recurrence is extremely common and disease progression is severely crippling for patients.</jats:p> <jats:p>Expression of activated tyrosine kinase receptors and downstream pathways has been observed, including PDGFRβ and EGFR. Although some clinical responses have been obtained with Imatinib, also in combination with Sirolimus, and with Erlotinib, these treatments cannot eradicate the disease, and there is a strong need for new effective therapies.</jats:p> <jats:p>Only a handful of chordoma cell lines are available today and the paucity of in vitro models has so far limited the identification of new molecular targets and the assessment of the efficacy of small molecules inhibitors on chordoma cells proliferation.</jats:p> <jats:p>Here we present the establishment and the characterization of the new Chor-IN-1 chordoma cell line from a recurrent sacral tumor of a patient previously treated with Imatinib and radiotherapy. The cell line has a very slow growth rate, as normally observed for this type of tumors, and displays the typical chordoma physaliferous morphology. The karyotype is indicative of a single population and the Short Tandem Repeat (STR) profile is unique and 100% identical to that of the original tumor sample. The cell line expresses the most relevant chordoma biomarkers, like the product of the “T” gene Brachyury, CD24 and Cytoketatin 19. The non synonymous rs2305089 polymorphism in the “T” gene, associated with chordoma predisposition, was identified in the Chor-IN-1, as well as in the UCH-1 and UCH-2 chordoma reference cell lines.</jats:p> <jats:p>To further characterize the new cell line, its genetic background and transcriptional profile, with particular focus on kinases, was analysed by a Next Generation Sequencing (NGS) approach, in parallel with UCH-1 and UCH-2, to identify common and unique cancer related features.</jats:p> <jats:p>Finally, the cell line was characterized for its sensitivity to selected kinase inhibitor drugs already approved or in clinical testing, in parallel with the control cell lines. Among the several EGFR inhibitors tested, Afatinib resulted generally the most active, suggesting that treatment with this drug may represent a valuable therapeutic approach in chordoma.</jats:p> <jats:p>In conclusion, we report the establishment and in depth characterization of a new chordoma cell line that, retaining all the typical features of chordomas, represents a useful tool for the identification of candidate new druggable targets, or active drugs for chordoma therapy.</jats:p> <jats:p>Citation Format: Paola Magnaghi, Roberta Bosotti, Nadia Amboldi, Liviana Cozzi, Alessio Somaschini, Silvia Stacchiotti, Fabio Bozzi, Elena Tamborini, Elena Conca, Silvana Pilotti, Marco A. Pierotti, Sebastiano Di Bella, Carlo Cusi, Dario Ballinari, Arturo Galvani, Barbara Salom, Antonella Isacchi. Establishment and characterization of the new sacral chordoma cell line Chor-IN-1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 74. doi:10.1158/1538-7445.AM2015-74</jats:p>
  • Access State: Open Access