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Phenotypic knockout of VEGF-R2 and Tie-2 with an intradiabody reduces tumor growth and angiogenesis in vivo.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Jendreyko, Nina Popkov, Mikhail Rader, Christoph |
| Copyright Year | 2005 |
| Abstract | The endothelial cell receptor-tyrosine kinases, VEGF receptor 2 (VEGF-R2) and Tie-2, and their ligands, vascular endothelial growth factor (VEGF) and angiopoietins 1 and 2, respectively, play key roles in tumor angiogenesis. Several studies suggest that the VEGF receptor pathway and the Tie-2 pathway are independent and essential mediators of angiogenesis, leading to the hypothesis that simultaneous interference with both pathways should result in additive effects on tumor growth. In this study, a human melanoma xenograft model (M21) was used to analyze the effects of simultaneous intradiabody depletion of vascular endothelial growth receptor-R2 and Tie-2 on tumor angiogenesis and tumor xenograft growth. The intradiabodies were expressed from recombinant adenovirus delivered through subtumoral injection. Blockade of both VEGF-R2 and Tie-2 pathways simultaneously or the VEGF receptor pathway alone resulted in a significant inhibition of tumor growth and tumor angiogenesis (92.2% and 74.4%, respectively). In addition, immunohistochemical staining of intradiabody-treated tumors demonstrated a decreased number of tumor-associated blood vessels versus control treatment. Previous studies with intrabodies had demonstrated that the Tie-2 receptor pathway was essential for tumor growth. The simultaneous blockade of the VEGF and Tie-2 pathways resulted in effective inhibition of tumor growth and demonstrated the potential of simultaneous targeting of multiple pathways as a therapeutic strategy. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.scripps.edu/barbas/pdf/jendreykoPNAS05.pdf |
| PubMed reference number | 15928093v1 |
| Volume Number | 102 |
| Issue Number | 23 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenoviruses Angiopoietins Blood Vessel Endothelial Growth Factors Ligands Neoplasms Recombinants Staining method Tumor Angiogenesis Tyrosine Vascular Endothelial Growth Factor Receptor-2 Xenograft type of graft bevacizumab cellular targeting |
| Content Type | Text |
| Resource Type | Article |
