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, Ray Nagle, Lee 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
StatePublished - May 1 2015

Keywords

  • malignant fibrous histiocytoma
  • radiation-induced
  • sarcoma

ASJC Scopus subject areas

  • Surgery
  • Oncology

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    Lang, J., Zhu, W., Nokes, B., Sheth, G., Novak, P., Fuchs, L., Watts, G., Futscher, B., Mineyev, N., Ring, A., Lebeau, L., Nagle, R., & Cranmer, L. (2015). Characterization of a novel radiation-induced sarcoma cell line. Journal of Surgical Oncology, 111(6), 669-682. https://doi.org/10.1002/jso.23860