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

Meyer, Stefanie and Hafner, Christian and Guba, Markus and Flegel, Stefanie and Geissler, Edward K. and Becker, Bernd and Koehl, Gudrun E. and Orso, Evelyn and Landthaler, Michael and Vogt, Thomas (2005) Ephrin-B2 overexpression enhances integrin-mediated ECM-attachment and migration of B16 melanoma cells. INTERNATIONAL JOURNAL OF ONCOLOGY, 27 (5). pp. 1197-1206. ISSN 1019-6439, 1791-2423

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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 B 16 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 Bl-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.

Item Type: Article
Uncontrolled Keywords: PROTEIN-TYROSINE KINASES; FOCAL-ADHESION-KINASE; EPH RECEPTORS; B LIGANDS; FAMILY; ACTIVATION; REVERSE; PHOSPHORYLATION; TUMORIGENICITY; MORPHOGENESIS; ephrin-B2; melanoma; matrix interaction; migration; invasion; metastasis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Dermatologie und Venerologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 23 Apr 2021 11:03
Last Modified: 23 Apr 2021 11:03
URI: https://pred.uni-regensburg.de/id/eprint/35473

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