Characterization of a novel radiation-induced sarcoma cell line

Julie Lang, Weizhu Zhu, Brandon Nokes, Grishma Sheth, Petr Novak, Laura Fuchs, George Watts, Bernard Futscher, Neal Mineyev, Alexander Ring, Lauren Lebeau, Raymond B Nagle, Lee D Cranmer

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. Methods We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. Results Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90% of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. Conclusion Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS.

Original languageEnglish (US)
Pages (from-to)669-682
Number of pages14
JournalJournal of Surgical Oncology
Volume111
Issue number6
DOIs
Publication statusPublished - May 1 2015

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Keywords

  • malignant fibrous histiocytoma
  • radiation-induced
  • sarcoma

ASJC Scopus subject areas

  • Surgery
  • Oncology

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