Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis

A murine mRNA (provisionally called 2ar) is described whose abundance is greatly increased by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate both in JB6 epidermal cells in vitro and in epidermis in vivo. We have previously shown induction of 2ar in epidermal or fibroblast cell lines by tumor promoters, growth factors, and transformation with H-ras. The 2ar mRNA appears to be derived from a single copy gene. It encodes the mouse homolog of rat osteopontin, a 41.5-kDa glycosylated bone phosphoprotein that binds to fibroblasts and osteosarcoma cells and to hydroxylapatite (bone matrix). The rat and mouse sequences are 84% identical at the amino acid level and 87% identical at the nucleotide level. Many of the primary structural features are conserved, including a run of 9-10 aspartic residues and a Gly-Arg-Gly-Asp-Ser cell adhesion sequence. Antiserum raised against portions of the predicted polypeptide immunoprecipitated proteins of apparent Mr 55,000-70,000 both from reticulocyte lysates containing the translation products of hybrid-selected mRNA and from cell culture medium containing metabolically labeled proteins secreted by JB6 cells. The results presented here demonstrate that osteopontin is identical to a transformation-associated phosphoprotein whose level of expression by cultured cells and abundance in human sera has been correlated with tumorigenicity. These results suggest a role for osteopontin in carcinogenesis. The murine version of osteopontin has been given the formal name "secreted phosphoprotein 1" and the designation spp.