1: Biol Chem. 2003 Jul;384(7):1073-83. 

Ovarian cancer cell proliferation and motility is induced by engagement of
integrin alpha(v)beta3/Vitronectin interaction.

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

Department of Obstetrics and Gynecology, Clinical Research Unit, Technical
University Munich, D-81675 Munich, Germany.

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 alpha(v)beta3, 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 alpha(v)beta3 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 alpha(v)beta3 and was accompanied by rapid and transient
tyrosine-phosphorylation of p44(erk-1)/p42(erk-2) mitogen-activated protein
kinase. Moreover, overexpression of alpha(v)beta3 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 alpha(v)beta3/VN
interaction, by cDNA expression microarray analysis we identified altered mRNA
levels of c-myc, epidermal growth factor receptor (EGF-R), transcription factor
Fra-1, prothymosin-alpha (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.

PMID: 12956424 [PubMed - indexed for MEDLINE]


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