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Ovarian Cancer Cell Proliferation and Motility is Induced by Engagement of Integrin alphavß3/ Vitronectin Interaction.
Biol. Chem. 384, 1073-1083 (2003)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
cDNA expression microarray Cell adhesion Differential gene expression Extracellular matrix Focal adhesion RGD peptides
ISSN (print) / ISBN
1431-6730
e-ISSN
1437-4315
Zeitschrift
Biological Chemistry
Quellenangaben
Band: 384,
Heft: 7,
Seiten: 1073-1083
Verlag
de Gruyter
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pathology (PATH)