title: Ovarian cancer cell proliferation and motility is induced by engagement of integrin alpha(v)beta3/Vitronectin interaction.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Clinical Research Unit, Technical University Munich, D-81675 Munich, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hapke
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Birgit
authors.initials: B
authors.lastname: Luber
authors.forename: Anke
authors.initials: A
authors.lastname: Benge
authors.forename: Peter
authors.initials: P
authors.lastname: Hutzler
authors.forename: Heinz
authors.initials: H
authors.lastname: Höfler
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmitt
authors.forename: Ute
authors.initials: U
authors.lastname: Reuning
mesh_terms: D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D019096:Vitronectin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D039302:Integrin alphaVbeta3; D019096:Vitronectin