Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth
AUTOR(ES)
Noren, Nicole K.
FONTE
National Academy of Sciences
RESUMO
Receptor tyrosine kinases of the Eph family are up-regulated in different types of cancer. EphB4 and its ligand ephrin-B2 have been linked to breast cancer, but little is known about how this receptor–ligand complex may contribute to oncogenesis. The Eph receptors transmit forward signals via their kinase domain and reverse signals via their transmembrane ephrin-B ligands. Therefore, we used EphB4 that were lacking the kinase domain and tagged with EGFP (EphB4ΔC-EGFP) to differentiate between EphB4 and ephrin-B2 signaling. Interestingly, we found that expression of EphB4ΔC-EGFP in breast cancer cells increases tumor growth in a mouse xenograft model. Given the undetectable EphB4 activation in the tumor cells, dominant negative effects of EphB4ΔC-EGFP are unlikely to explain the increased tumor growth. Examination of the tumors revealed that ephrin-B2 is primarily expressed in the vasculature and that the EphB4ΔC-EGFP tumors have a higher blood content than control tumors, concomitant with increased size of blood vessels. In support of an effect on the vasculature, the extracellular domain of EphB4 attracts endothelial cells in vitro and stimulates endothelial cell invasion, survival, and proliferation, all crucial factors for angiogenesis. These results support a model in which EphB4 promotes tumor growth by stimulating angiogenesis through ephrin-B2.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=397426Documentos Relacionados
- Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis
- The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth
- Receptor protein tyrosine kinase EphB4 is up-regulated in colon cancer
- Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2
- EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures