Angiocidin inhibitory peptides decrease tumor burden in a murine colon cancer model.
BACKGROUND
We have recently developed two inhibitory peptides that target angiocidin, a key mediator of tumor progression and angiogenesis. In this study, we investigate the expression of angiocidin in human colon cancer specimens and evaluate the therapeutic efficacy of our angiocidin inhibitory peptides.


METHODS
We created a colon cancer tissue array containing primary tumor, normal colon, negative and positive lymph nodes, and liver metastases (when available) from 159 consecutive colon cancer specimens. Angiocidin expression was determined by immunohistochemistry. The efficacy of 6-mer and 25-mer angiocidin inhibitory peptides was determined in a murine model of human colon cancer. Treatment efficacy was based on primary tumor volume and measures of tumor burden, including internal disease score and health score. Western blots were used to determine angiocidin expression in xenografts.


RESULTS
Eighty-nine percent of primary tumors and 91% of positive lymph nodes expressed angiocidin. Normal colon was negative in 94% of specimens, and normal lymph nodes were negative or weakly positive in 79% of specimens. All liver metastases were positive for angiocidin. Animals in both peptide treatment groups showed improvement in health score and internal disease score compared with control animals (P = 0.001). Treatment with 6-mer and 25-mer peptide resulted in 3-fold and 16-fold reductions, respectively, in primary tumor volume (P = 0.001). Angiocidin expression in primary tumors of peptide-treated mice correlated with tumor burden (P < 0.05).


CONCLUSIONS
Angiocidin is overexpressed in human colon cancer specimens. Angiocidin-inhibitory peptides are well tolerated in vivo and effectively reduce primary tumor volume and tumor burden in human colon cancer xenografts.
Liebig
Catherine
C
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
Agarwal
Neeti
N
Ayala
Gustavo E
GE
Verstovsek
Gordana
G
Tuszynski
George P
GP
Albo
Daniel
D
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D016601:RNA-Binding Proteins; D013154:Spleen / Q000473:pathology; D019700:Thrombospondin 1 / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002352:Carrier Proteins; C498506:PSMD4 protein, human; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D019700:Thrombospondin 1; C494028:cysteinyl-seryl-valyl-threonyl-cysteinyl-glycine; D046988:Proteasome Endopeptidase Complex