Overexpression of integrin αv promotes human osteosarcoma cell populated collagen lattice contraction and cell migration

Abstract

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.

Platelet-Derived Growth Factor BB–Mediated Normalization of Dermal Interstitial Fluid Pressure After Mast Cell Degranulation Depends on β3 but Not β1 Integrins

“…16,17 Furthermore, forced expression of the ␣V subunit in human osteosarcoma cells that lack endogenous expression of the collagen-binding integrin ␣2␤1 promotes collagen gel contraction by these cells. 18 These findings are consistent with an earlier report suggesting that the ␣V␤3 integrin, under certain conditions, may function as a collagen receptor that mediates collagen gel contraction. 19 Consistent similarities in the control of cell-mediated collagen-gel contraction in vitro and P IF and edema formation in vivo have been observed.…”

Calmodulin‐myosin light chain kinase inhibition changes fibroblast‐populated collagen lattice contraction, cell migration, focal adhesion formation, and wound contraction

“…Transmembrane integrin receptors, α2β1, α1β1, α11β1, and αvβ3 that associate with collagen, are pivotal to collagen organization 23,24 . The expression of α2β1, α1β1, or αvβ3 integrin receptors are involved in FPCL contraction 25–31 . The same mechanism required for cell migration is the proposed cellular mechanism needed for aligning collagen fibrils into thicker collagen fiber arrays.…”

“…23,24 The expression of a2b1, a1b1, or avb3 integrin receptors are involved in FPCL contraction. [25][26][27][28][29][30][31] The same mechanism required for cell migration is the proposed cellular mechanism needed for aligning collagen fibrils into thicker collagen fiber arrays.…”

Mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold

“…FPCLs were constructed as previously described [28,29]. In brief, FPCLs were prepared in triplicate by combining the following materials in the corresponding order: 50 mL of 5xPBS (pH 8.5, 23 C) was combined with 200 mL bovine type I collagen (6 mg/ml, pH 5, 23 C) (Nutragen, Advanced Biomatrix, San Diego, CA, USA), and 750 mL cell suspension (590,000 cells/mL).…”