Interaction between protein 4.1R and spectrin heterodimers.

Defects or deficiencies in red cell membrane skeletal proteins often undermine the integrity and stability of the plasma membrane, and consequently cause hereditary hemolytic anemias. Genetic and biochemical studies have revealed a complicated picture of the organization of the membrane skeleton, within which α-/ß-spectrin heterodimers form a protein lattice. By stabilizing the red cell membrane skeleton, the erythroid protein 4.1R greatly contributes to connecting and regulating the interaction among spectrins, actin filaments and integral proteins on the plasma membrane. In this study, we demonstrated the direct interaction between 4.1R and α-/ß-spectrin. The results provide novel insights into the stoichiometry of 4.1R with spectrin, and demonstrate for the first time that the binding ratio of 4.1R to spectrin heterodimers is approximately 5.

Overexpression of human osteopontin increases cell proliferation and migration in human embryo kidney-293 cells.

Malignant tumors are characterized by dysregulated cell growth and the metastasis of secondary tumors. Numerous studies have documented that osteopontin (OPN) plays a key role in regulating tumor progression and metastasis. Here, we show that the overexpression of OPN in human embryo kidney-293 cells significantly increases both the level of cell proliferation, by provoking the G(1)/S transition, and the level of cell migration in vitro. These findings suggest that augmented OPN contributes to cell growth and motility. Inhibiting OPN or the pathway it stimulates may therefore represent a novel approach for the treatment of primary tumors and associated metastases.

The inhibition of in vivo tumorigenesis of osteosarcoma (OS)-732 cells by antisense human osteopontin RNA.

Osteopontin (OPN) is a secreted, non-collagenous, sialic acid-rich protein which functions by mediating cell-matrix interactions and cellular signaling via binding with integrins and CD44 receptors. An increasing number of studies have shown that OPN plays an important role in controlling cancer progression and metastasis. OPN was found to be expressed in many human cancer types, and in some cases, its over-expression was shown to be directly associated with poor patient prognosis. In vitro cancer cell line and animal model studies have clearly indicated that OPN can function in regulating the cell signaling that ultimately controls the oncogenic potential of various cancers. Previous studies in our laboratory demonstrated that OPN is highly expressed in human osteosarcoma (OS) cell line OS-732. In this study, we successfully reduced the tumorigenecity of OS-732 cells xenotransplanted into nude mice, using the antisense human OPN (hOPN) RNA expression vector.