Evaluation of Novel Agents Which Target Neovasculature of Breast Tumors
Abstract
The unique fusion toxin VEGF121/rGel specifically kills both log-phase and confluent vascular endothelial cells expressing the KOR receptor for VEGF (PNAS 99:7866 2002). We have discovered 22 unique genes consistently up-regulated in endothelial cells treated with VEGF121/rGel (confirmed by Western and RT-PCR). VEGF121/rGel (i.v.) treatment against an orthotopic breast model resulted in significant delay of tumor growth by 50%. In addition tumors completely regressed in 3/6 (50%) of treated mice. In the metastatic breast model treatment with VEGF121/rGel reduced both the number and area of lung foci by 58% and 50% respectively. Immunohistochemical analysis demonstrated that VEGF121/rGel targeted lung tumor vasculature but not normal vasculature. In addition the number of blood vessels per mm2 in metastatic foci was 198 + 37 versus 388 + 21 for treated and control respectively. Approximately 62% of metastatic colonies from the VEGF/rGel treated group had <10 vessels/colony compared to 23% in the control group. Metastatic foci had a 3 fold lower Ki-67 labeling index compared to control tumors. This suggests that VEGF121/rGel has impressive anti-tumor activity in breast cancer. In addition VEGF121/rGel prevented osteolytic lesions in a prostate cancer bone tumor model and inhibited new bone formation in an ex vivo model with murine calvaria. Thus VEGF121/rGel may be useful in inhibiting breast cancer skeletal metastases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA456134
Entities
People
- Michael G. Rosenblum
Organizations
- The University of Texas MD Anderson Cancer Center