Delineating the Effect a Novel Anti-VEGF-A Therapy Has on the Lymphatic System of Immunocompetent Tumor-Bearing Mice
Abstract
Despite intense research efforts, cancer remains the second leading cause of death in the United States. Mortality is a seldom caused by primary tumors, but rather by the effect of metastases on distant organs. The lymphatic system serves as a common route of metastasis for many cancers of epithelial origin. There is growing evidence that lymphangiogenesis, the sprouting of new lymphatics from pre-existing lymphatics, facilitates the dissemination of cancer. Interestingly, the growth factor VEGF-A stimulates lymphangiogensis; however, the underlying mechanisms have not been fully defined. To achieve a better understanding of VEGF- A's function in biology, our lab helped develop a novel anti-VEGF-A antibody (r84) that specifically blocks mouse and human VEGF-A activation of VEGFR2, but not VEGFR1. Here, we show for the first time that inhibition of VEGF-A activation of VEGFR2 on lymphatic endothelial cells (LECs) suppresses lymphangiogenesis by blocking ERK1/2 driven LEC proliferation and migration. Furthermore, we demonstrate that although LECs are distinct from BECs, they respond to VEGF-A similarly. Therefore, therapeutic agents targeting the VEGF-A/VEGFR2 axis could be useful to prevent the pathological formation of blood and lymphatic vessels.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2011
- Accession Number
- ADA552077
Entities
People
- Michael T. Dellinger
Organizations
- University of Texas at Dallas