Eph receptors mediate short-range cell-to-cell
communication by binding membrane-bound ephrin ligands
expressed by neighbouring cells. They function in an
amazing variety of developmental and adult processes
like cell migration, axon guidance and topographic
mapping, segmental patterning, synapse morphology and
synapse plasticity, angiogenesis and tumorigenesis. The
main goal of this project is to study the Eph and ephrin
system in the context of tumor angiogenesis and tumor
cell behaviour. We will study the process of
tumour-induced blood vessel formation with focus on
endothelial cell-endothelial cell and tumour cell-
endothelial cell communication. Cell adhesion and
repulsion mediated by Eph and ephrins in various
angiogenesis assays involving glioma and endothelial
cells will be analyzed. We plan to do loss-of-function
experiments by isolating endothelial cells from
conditional mice lacking ephrinB2 as well as from
ephrinB2 signaling mutant mice. In order to study the
requirements for Eph/ephrin signaling in the tumor cells
for tumor growth and invasiveness in vitro and in vivo,
murine gliomas with mutated ephrinB2 or lacking ephrinB
ligands will be generated by isolation and
transformation of astrocytes from genetically engineered
mice. |
Bruhl, T, Urbich C, Aicher D, Acker-Palmer A,
Zeiher AM, Dimmeler S: Homeobox A9 transcriptionally
regulates the EphB4 receptor in endothelial cell
migration and tube formation. Circ Res 94:
743-51, 2004
Palmer A, Klein R: Multiple roles of ephrins in
morphogenesis, neuronal networking, and brain function. Genes Dev 17: 1429-50, 2003
Zimmer M, Palmer A, Köhler J, Klein R:
Contact-mediated repulsion by ephrinB ligands and EphB
receptors requires bi-directional endocytosis. Nature
Cell Biol 5: 869-78, 2003
|
palmer(at)neuro.mpg.de