Elevated expression of secreted phosphoprotein I (osteopontin, 2ar) as a consequence of neoplastic transformation

Abstract

Several lines of evidence have recently been presented indicating that proteins previously referred to as Mr 62,000-67,000 transformation-associated secreted phosphoprotein, 2ar, osteopontin, bone sialoprotein I, and 44K Dal bone phosphoprotein are all very likely encoded by the same gene. We have found that markedly elevated expression of this protein, which henceforth is referred to as secreted phosphoprotein I (Sppl) closely correlates with neoplastic transformation of a variety of cell types and that patients with advanced stage metastatic cancers have elevated levels of Sppl in their blood. Moreover, Sppl expression is induced in mouse epidermal cells in vitro and mouse epidermis in vivo with the tumor promoter TPA (Craig et al, J. Biol. Chem. 264: 9682-9689, 1989). Sppl amino acid sequence deduced from cDNA nucleotide sequence (Oldberg et al, Proc. Natl. Acad Sci. U.S.A. 83: 8819-8823, 1986) contains the GRGDS cell-binding sequence which is known to be important for cell attachment to several adhesive proteins found in extracellular matrices. Because of the presence of the GRGDS cell-binding sequence in Sppl, it is probable that abnormally high expression of this soluble protein by tumor cells has important consequences for interactions between tumor cells and the host tissue matrix.