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 Citations (Scopus)

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

Fingerprint

Gelatinases
Thrombospondin 1
Sarcoma
Neoplasms
Peptides
Osteosarcoma
Up-Regulation
CD36 Antigens
Tissue Inhibitor of Metalloproteinases
Cell Line
Matrix Metalloproteinase Inhibitors
Stromal Cells

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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

The role of angiocidin in sarcomas. / Liebig, Catherine; Wilks, Jonathan A.; Feig, Barry W.; Wang, Thomas N.; Wilson, Mariya; Herdman, Ann V.; Albo, Daniel.

In: Cancer, Vol. 115, No. 22, 15.11.2009, p. 5251-5262.

Research output: Contribution to journalArticle

Liebig, C, Wilks, JA, Feig, BW, Wang, TN, Wilson, M, Herdman, AV & Albo, D 2009, 'The role of angiocidin in sarcomas', Cancer, vol. 115, no. 22, pp. 5251-5262. https://doi.org/10.1002/cncr.24568
Liebig C, Wilks JA, Feig BW, Wang TN, Wilson M, Herdman AV et al. The role of angiocidin in sarcomas. Cancer. 2009 Nov 15;115(22):5251-5262. https://doi.org/10.1002/cncr.24568
Liebig, Catherine ; Wilks, Jonathan A. ; Feig, Barry W. ; Wang, Thomas N. ; Wilson, Mariya ; Herdman, Ann V. ; Albo, Daniel. / The role of angiocidin in sarcomas. In: Cancer. 2009 ; Vol. 115, No. 22. pp. 5251-5262.
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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.",
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N2 - 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.

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