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Published on: September 30, 2016
Angiocidin inhibitory peptides decrease tumor burden in a murine colon cancer model
Catherine Liebig1, Neeti Agarwal, Gustavo E Ayala
1Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
Introduction:
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.
Insights
Angiocidin, a key factor in tumor growth, is highly expressed in human colon cancer. New inhibitory peptides effectively reduced tumor size and burden in preclinical models, showing promise for colon cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Angiogenesis and tumor progression are significantly influenced by angiocidin.
- Two novel inhibitory peptides targeting angiocidin have been developed.
- This study investigates angiocidin expression in human colon cancer and peptide efficacy.
Purpose of the Study:
- To determine angiocidin expression levels in human colon cancer tissues.
- To evaluate the therapeutic potential of angiocidin inhibitory peptides in a colon cancer model.
Main Methods:
- A colon cancer tissue array from 159 specimens was analyzed for angiocidin expression via immunohistochemistry.
- The efficacy of 6-mer and 25-mer angiocidin inhibitory peptides was assessed in a murine colon cancer model.
- Tumor volume, burden (internal disease and health scores), and xenograft angiocidin expression were measured.
Main Results:
- Angiocidin was overexpressed in 89% of primary colon tumors and 91% of positive lymph nodes; all liver metastases were positive.
- Peptide treatment significantly improved health and internal disease scores in mice compared to controls (P = 0.001).
- Primary tumor volume was reduced by 3-fold and 16-fold with 6-mer and 25-mer peptides, respectively (P = 0.001).
Conclusions:
- Angiocidin is significantly overexpressed in human colon cancer, indicating its role in the disease.
- Angiocidin-inhibitory peptides demonstrate good in vivo tolerability.
- These peptides effectively reduce tumor volume and burden in preclinical models of human colon cancer.
