Overexpression of integrin alphav promotes human osteosarcoma cell populated collagen lattice contraction and cell migration.
Cells attach and interact with the extracellular matrix (ECM) through heterodimeric alphabeta integrin receptors. Specifically, the promiscuous alphavbeta3 integrin and the alpha2beta1 integrin receptors engage numerous matrix components to influence cell adhesion, cell motility, and matrix organization. However, the role of alphav integrin mediating cell-collagen interactions is not clear. In the in vitro cell populated collagen lattice (PCL), a model of cell-matrix interaction, integrin receptors play a role in lattice contraction. To elucidate alphav integrins' effects on cell-collagen interactions, human osteosarcoma (HOS) cells were transfected with alphav integrin (alphav-pcDNA 3.1+). Control HOS cells were transfected with pcDNA 3.1+ vector alone. HOS-alphav cell PCLs contracted to a greater degree than control HOS cell PCLs (P < or = 0.0001). RT-PCR revealed that HOS-alphav cells express both beta1 and beta3 integrins, indicating that alphav has the potential to form a partnership with either beta1 or beta3 integrin. The alphavbeta3 specific inhibitory antibody LM609 significantly retarded HOS-alphav cell PCL contraction (P < or = 0.001), suggesting that alphavbeta3 promotes enhanced HOS-alphav cell PCL contraction. When plated on plastic, control HOS cells show greater elongation compared to HOS-alphav cells. In addition, HOS-alphav cells migrated faster and to a greater degree than control HOS cells (P < or = 0.0001). The possibility that enhanced HOS-alphav cell migration and HOS-alphav cell PCL contraction was caused by increased myosin ATPase activity was examined. HOS-alphav cells showed less myosin ATPase activity than control HOS cells, by an ATP cell contraction bioassay. The enhancement of HOS-alphav cell migration and lattice contraction appears unrelated to increased myosin ATPase activity.
Levinson
Howard
H
Division of Plastic Surgery, M.S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA. hlev1@yahoo.com
Hopper
James E
JE
Ehrlich
H Paul
HP
D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000502:physiology; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039564:Integrin alphaV / Q000502:physiology*; D007700:Kinetics; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039564:Integrin alphaV; D012333:RNA, Messenger; D003094:Collagen; D009218:Myosins