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A comparison of antiangiogenic therapies for the prevention of liver metastases.
- Source :
-
The Journal of surgical research [J Surg Res] 2006 Mar; Vol. 131 (1), pp. 97-104. Date of Electronic Publication: 2005 Oct 20. - Publication Year :
- 2006
-
Abstract
- Angiogenesis is essential for solid tumor growth. Although successful antiangiogenic therapies have been demonstrated in animal models, a systematic comparison of the efficacy of different antiangiogenic factors has not been described in the hepatic environment. To address this issue, CT26 murine colon carcinoma cells were transfected with retroviral vectors encoding murine endostatin (mEndostatin), human angiostatin (hAngiostatin), murine-soluble vascular endothelial growth factor receptor-2, (msFlk-1), or murine-soluble Tie2 (msTie2). The transfected cells were then subjected to another round of transfection with a luciferase cDNA-encoding retroviral vector. Expression of these putative antiangiogenic proteins inhibited the proliferation of human umbilical vein endothelial cells in vitro but not tumor cells. To examine effects on tumor growth in vivo, modified cells were delivered via intrasplenic injection into BALB/c mice to induce liver metastases. Tumor burden was measured weekly by bioluminescence. Growth of hepatic metastases in vivo was significantly reduced in mice that were administered cells expressing msTie2 (76% reduction compared with control cells 21 days after intrasplenic inoculation; P < 0.05). Similar results were observed with cells that expressed msFlk-1 and hAngiostatin. However, expression of mEndostatin had no significant effect on the growth of liver metastases compared with control animals. These findings indicate that multiple antiangiogenic pathways are necessary for the growth of hepatic metastases, and each of these pathways is a potential clinically relevant antiangiogenic target for the treatment of this disease.
- Subjects :
- Angiostatins genetics
Angiostatins physiology
Animals
Cell Proliferation
Endostatins genetics
Endostatins physiology
Endothelial Cells physiology
Female
Mice
Mice, Inbred BALB C
Neoplasms, Experimental
Receptor, TIE-2 genetics
Receptor, TIE-2 physiology
Transfection
Tumor Cells, Cultured
Vascular Endothelial Growth Factor Receptor-2 genetics
Vascular Endothelial Growth Factor Receptor-2 physiology
Angiogenesis Inhibitors physiology
Colonic Neoplasms pathology
Liver Neoplasms prevention & control
Liver Neoplasms secondary
Neovascularization, Pathologic
Subjects
Details
- Language :
- English
- ISSN :
- 0022-4804
- Volume :
- 131
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of surgical research
- Publication Type :
- Academic Journal
- Accession number :
- 16242720
- Full Text :
- https://doi.org/10.1016/j.jss.2005.09.008