Ovarian cancer cell proliferation and motility is induced by engagement of integrin αvβ3/vitronectin interaction

During tumor metastasis, a finetuned balance between the formation and loosening of adhesive cell contacts has to occur, a process based on the regulated expression of integrins. Human ovarian OVMZ-6 cancer cells express the integrin alphavbeta3, which associates with vitronectin (VN) and correlates with ovarian cancer progression. Adhesion and spreading of OVMZ 6 cells on VN was accompanied by the formation of focal adhesion contacts and the recruitment of activated tyrosinephosphorylated focal adhesion kinase. Cultivation of OVMZ-6 cells on VN resulted in a significantly induced cell proliferation. This VN effect could be mimicked by cultivating cells on the immobilized alphavbeta3-directed peptide cycloArgGlyAspDPhe Val (cRGDfV). VNdependent OVMZ-6 cell adhesion and proliferation was significantly enhanced by overexpression of alphavbeta3, and was accompanied by rapid and transient tyrosinephosphorylation of p44erk 1/p42erk 2 mitogenactivated protein kinase. Moreover, overexpression of alphavbeta3 and OVMZ-6 cell attachment to VN increased cell motility up to 5-fold accompanied by prominent changes in cytoskeletal organization and cell morphology. Upon alphavbeta3/VN interaction, by cDNA expression microarray analysis we identified altered mRNA levels of cmyc, epidermal growth factor receptor (EGFR), transcription factor Fra-1, prothymosin-alpha (PTMA), integrinlinked 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.