The role of angiocidin in sarcomas

Catherine Liebig, Jonathan A. Wilks, Barry W. Feig, Thomas N. Wang, Mariya Wilson, Ann V. Herdman, Daniel Albo

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

BACKGROUND: Angiocidin, first identified as a tumor-associated thrombospondin-1 (TSP-1) receptor, is a key mediator of tumor progression. TSP-1, an extracellular protein produced by stromal cells, up-regulates gelatinases and tumor cell invasion in epithelial malignancies. The authors recently developed 2 angiocidininhibitory peptides that block angiocidin-TSP-1 binding. They hypothesized that angiocidin mediates increased gelatinase expression and tumor cell invasion in sarcomas through its interaction with TSP-1. METHODS: Angiocidin, TSP-1, and gelatinase expression was evaluated in low-grade and high-grade sarcoma specimens. The authors established 3 distinct cell lines from a patient with an extraskeletal osteosarcoma: EXOS-N (normal mesenchymal), EXOS-P (primary osteosarcoma), and EXOS-M (lung metastasis). Each was evaluated for angiocidin, gelatinase, and gelatinase inhibitor (tissue inhibitors of metalloproteinase) expression and for invasive capacity. Their responsiveness to TSP-1 was determined. The role of angiocidin in up-regulating gelatinase expression and invasion was studied using the authors' angiocidin-inhibitory peptides. RESULTS: Expression of angiocidin, TSP-1, and gelatinases correlated with tumor grade. Angiocidin expression, gelatinase activity, and invasiveness in the EXOS cell lines correlated with phenotype; EXOS-N cells did not express angiocidin or gelatinases and were not invasive; EXOS-M cells were 5 times more invasive than EXOS-P cells and exhibited greater angiocidin and gelatinase expression. EXOS cell gelatinase activity and invasiveness increased 4- to 5-fold in response to TSP-1. Inhibition of angiocidin with the authors' inhibitory peptides blocked TSP-1-promoted increases in gelatinase activity and tumor cell invasion. CONCLUSIONS: Angiocidin promotes gelatinase up-regulation and tumor cell invasion in sarcomas. Angiocidin-inhibitory peptides are potent inhibitors of sarcoma cell invasion in vitro, suggesting a potential therapeutic role for these peptides in the treatment of sarcomas.

Original languageEnglish (US)
Pages (from-to)5251-5262
Number of pages12
JournalCancer
Volume115
Issue number22
DOIs
StatePublished - Nov 15 2009
Externally publishedYes

Keywords

  • Angiocidin
  • Angiocidin-inhibitory peptide
  • CSVTCG
  • Extraskeletal osteosarcoma
  • Peptide therapy
  • Sarcomas
  • Thrombospondin-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Liebig, C., Wilks, J. A., Feig, B. W., Wang, T. N., Wilson, M., Herdman, A. V., & Albo, D. (2009). The role of angiocidin in sarcomas. Cancer, 115(22), 5251-5262. https://doi.org/10.1002/cncr.24568