Ephrin-B2 overexpression enhances integrin-mediated ECM-attachment and migration of B16 melanoma cells.

Abstract

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.

• Authors: Stefanie Meyer, Christian Hafner, Markus Guba, Stefanie Flegel, Edward K Geissler, Bernd Becker, Gudrun E Koehl, Evelyn Orsó, Michael Landthaler, Thomas Vogt
• Journal: International journal of oncology (Int J Oncol) Vol. 27 Issue 5 Pg. 1197-206 (Nov 2005) ISSN: 1019-6439 [Print] Greece
• PMID: 16211213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ephrin-B2

Topics

• Animals
• Cell Adhesion
• Cell Movement
• Ephrin-B2 (biosynthesis)
• Extracellular Matrix (physiology)
• Gene Expression Profiling
• Melanoma (pathology)
• Mice
• Neoplasm Invasiveness
• Neoplasm Metastasis (physiopathology)
• Pseudopodia (physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Skin Neoplasms (pathology)