A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model.

Abstract

Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned into prokaryotic expression plasmid pQE30 with a linker. The expression product recombinant VEGF-TF (rVEGF-TF) was purified and proved to have comparable enzyme activity to a commercial TF and the capability of specific binding to tumor vessels. Significant decrease of tumor growth was found in the mice administered with rVEGF-TF on Day 6 after initiated rVEGF-TF treatment (P<0.05), and the tumor masses in 2 of 10 mice were almost disappeared on Day 14 after the first treatment. In addition, valid thrombogenesis and tumor necrosis were observed in the tumor tissues injected with rVEGF-TF. Our results demonstrate that occlusion of tumor vasculature with rVEGF-TF is potentially an effective approach for cancer therapy.

• Authors: Feng-ying Huang, Yue-nan Li, Hua Wang, Yong-hao Huang, Ying-ying Lin, Guang-hong Tan
• Journal: Journal of Zhejiang University. Science. B (J Zhejiang Univ Sci B) Vol. 9 Issue 8 Pg. 602-9 (Aug 2008) ISSN: 1673-1581 [Print] China
• PMID: 18763309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Fusion Proteins
• Vascular Endothelial Growth Factor A
• Thromboplastin

Topics

• Animals
• Cell Line, Tumor
• Cloning, Molecular
• Colonic Neoplasms (blood supply, drug therapy, pathology)
• Disease Models, Animal
• Disease Progression
• Gene Expression
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Plasmids (genetics)
• Recombinant Fusion Proteins (genetics, isolation & purification, metabolism, therapeutic use)
• Thromboplastin (genetics, isolation & purification, metabolism, therapeutic use)
• Thrombosis (drug therapy, pathology)
• Vascular Endothelial Growth Factor A (genetics, isolation & purification, metabolism, therapeutic use)