1097-0142/asset/cover.gif?v=1&s=a7299bc18f075294c232ade468773cd0672bd470 "Cancer")
Fax: (713) 794-7352
1097-0142/asset/olbannerleft.gif?v=1&s=ca681f5719430b26e1bc15e9ea4c9fc0a7110104)
1097-0142/asset/olbannerright.gif?v=1&s=8142566facf7e76aef9be6c51162a2e920b3b9f9)
Original Article
You have full text access to this OnlineOpen article
The role of angiocidin in sarcomas
Article first published online: 24 JUL 2009
DOI: 10.1002/cncr.24568
Copyright © 2009 American Cancer Society
Additional Information
How to Cite
Liebig, C., Wilks, J. A., Feig, B. W., Wang, T. N., Wilson, M., Herdman, A. V. and Albo, D. (2009), The role of angiocidin in sarcomas. Cancer, 115: 5251–5262. doi: 10.1002/cncr.24568
Publication History
- Issue published online: 3 NOV 2009
- Article first published online: 24 JUL 2009
- Manuscript Accepted: 8 APR 2009
- Manuscript Revised: 4 APR 2009
- Manuscript Received: 23 DEC 2008
- Abstract
- Article
- References
- Cited By
Keywords:
- sarcomas;
- angiocidin;
- CSVTCG;
- peptide therapy;
- angiocidin-inhibitory peptide;
- extraskeletal osteosarcoma;
- thrombospondin-1
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 angiocidin-inhibitory 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. Cancer 2009. © 2009 American Cancer Society.