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Hapke, S.* ; Kessler, H.* ; Luber, B.* ; Benge, A.* ; Hutzler, P. ; Höfler, H.* ; Schmitt, M.* ; Reuning, U.*

Ovarian Cancer Cell Proliferation and Motility is Induced by Engagement of Integrin alphavß3/ Vitronectin Interaction.

Biol. Chem. 384, 1073-1083 (2003)
DOI
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During tumor metastasis, a fine-tuned balance between the formation and loosening of adhesive cell contacts has to occur, a process based on the regulated expression of integrins. Human ovarian OV-MZ-6 cancer cells express the integrin αvβ3, which associates with vitronectin (VN) and correlates with ovarian cancer progression. Adhesion and spreading of OV-MZ-6 cells on VN was accompanied by the formation of focal adhesion contacts and the recruitment of activated tyrosine-phosphorylated focal adhesion kinase. Cultivation of OV-MZ-6 cells on VN resulted in a significantly induced cell proliferation. This VN effect could be mimicked by cultivating cells on the immobilized αvβ3-directed peptide cyclo-Arg-Gly-Asp-D-Phe-Val (cRGDfV). VN-dependent OV-MZ-6 cell adhesion and proliferation was significantly enhanced by overexpression of αvβ3, and was accompanied by rapid and transient tyrosinephosphorylation of p44erk 1/p42erk 2 mitogen-activated protein kinase. Moreover, overexpression of αvβ3 and OV-MZ-6 cell attachment to VN increased cell motility up to 5-fold accompanied by prominent changes in cytoskeletal organization and cell morphology. Upon αvβ3/VN interaction, by cDNA expression microarray analysis we identified altered mRNA levels of cmyc, epidermal growth factor receptor (EGF-R), transcription factor Fra-1, prothymosin-α (PTMA), integrin-linked kinase (ILK), and the cell adhesion molecule SQM-1, candidates which are possibly involved in changes of the adhesive, migratory, and proliferative phenotype of human ovarian cancer cells.
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Publication type Article: Journal article
Document type Scientific Article
Keywords cDNA expression microarray Cell adhesion Differential gene expression Extracellular matrix Focal adhesion RGD peptides
Language german
Publication Year 2003
HGF-reported in Year 0
ISSN (print) / ISBN 1431-6730
e-ISSN 1437-4315
Journal Biological Chemistry
Quellenangaben Volume: 384, Issue: 7, Pages: 1073-1083 Article Number: , Supplement: ,
Publisher de Gruyter
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)
DOI 10.1515/BC.2003.120
Erfassungsdatum 2003-10-06
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