Ephrin-B2 overexpression enhances integrin-mediated ECM-attachment and migration of B16 melanoma cells.
Eph-receptor tyrosine kinases (Eph-RTKs) and their membrane-bound receptor-like ligands, the ephrins, represent a cell-cell signaling system that directs cellular migration during development. Differential expression in cancer suggests similar roles in tumor progression. We have previously shown that ephrin-B2 mRNA is overexpressed in advanced malignant melanomas (MM). In this study, immunohistochemistry revealed a most prominent expression of ephrin-B2 in the invasive front of advanced MM. Therefore, we addressed the question of whether ephrin-B2 signaling modulates MM cell migration and matrix interaction. Using a wild-type ephrin-B2-negative B16 mouse MM subclone we show that overexpression of ephrin-B2 leads to the formation of multiple lamellipodia, enhanced polymerisation of actin fibers, and induction of focal adhesion complexes with constitutive activation of focal adhesion kinase. Consequently, ephrin-B2-overexpressing B16 cells display a significant increase of beta1-integrin-mediated attachment to matrix components, preferentially laminin and fibronectin. As a further effect of ephrin-B2 overexpression, we observed an accelerated migration in both Boyden chamber invasion experiments as well as in in vitro scratch-wound assays. We conclude that ephrin-B2 can act as a major modulator of cell migration and matrix interactions of MM cells, which possibly contributes to the expansion and metastatic spread of MM in vivo.
Meyer
Stefanie
S
Department of Dermatology, University of Regensburg, D-93042 Regensburg, Germany. stefanie.meyer@klinik.uni-regensburg.de
Hafner
Christian
C
Guba
Markus
M
Flegel
Stefanie
S
Geissler
Edward K
EK
Becker
Bernd
B
Koehl
Gudrun E
GE
Orsó
Evelyn
E
Landthaler
Michael
M
Vogt
Thomas
T
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D036388:Ephrin-B2 / Q000096:biosynthesis*; D005109:Extracellular Matrix / Q000502:physiology*; D020869:Gene Expression Profiling; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology; D011554:Pseudopodia / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000473:pathology*
D036388:Ephrin-B2