The role of angiocidin in sarcomas.
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.
Liebig
Catherine
C
Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Wilks
Jonathan A
JA
Feig
Barry W
BW
Wang
Thomas N
TN
Wilson
Mariya
M
Herdman
Ann V
AV
Albo
Daniel
D
D018955:CD36 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D016601:RNA-Binding Proteins; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D019700:Thrombospondin 1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018955:CD36 Antigens; D002352:Carrier Proteins; C498506:PSMD4 protein, human; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D019700:Thrombospondin 1; D019714:Tissue Inhibitor of Metalloproteinases; C494028:cysteinyl-seryl-valyl-threonyl-cysteinyl-glycine; D018093:Gelatinases; D046988:Proteasome Endopeptidase Complex