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* Institut für Klinische Chemie und Laboratoriumsmedizin, 48149 Münster, Germany; and
Institut für Immunologie, Universität Witten/Herdecke, Witten 58453, Germany
1Correspondence: Institut für Klinische Chemie und Laboratoriumsmedizin, Albert-Schweitzer-Str. 33, 48149 Münster, Germany. E-mail: brandt{at}uni-muenster.de
Separate mechanisms for oncogenesis and metastasis have been postulated. We show here that prolonged and invasive cell migration, a key mechanism in cancer metastasis, is linked to c-erbB-2 signaling. Cell lines with c-erbB-2 and EGFR expression and transphosphorylation activity display a high transendothelial invasiveness in an endothelial-extracellular matrix model mimicking a capillary vessel wall in vitro. Tyrosine-phosphorylated c-erbB-2 receptors and EGFR are localized predominantly in areas of the cell with high membrane extension activity. On the molecular level, there is a subtle cross talk between the transmembrane signaling molecule c-erbB-2 and the actin cytoskeleton at multiple levels, including the generation of the second messenger PIP2 and the mobilization of the actin-regulatory protein gelsolin. Our data strongly suggest that c-erbB-2, especially in a heterodimer with EGFR, is closely involved in signaling pathways, inducing alterations in cell morphology that are required for a human breast cancer cell to become motile and conceivably metastatic.—Brandt, B. H., Roetger, A., Dittmar, T., Nikolai, G., Seeling, M., Merschjann, A., Nofer, J.-R., Dehmer-Möller, G., Junker, R., Assmann, G., Zaenker. K. S. c-erbB-2/EGFR as dominant heterodimerization partners determine a motogenic phenotype in human breast cancer cells.
Key Words: F-actin • gelsolin • epidermal growth factor • HUVEC
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