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Secreted phosphoprotein mrna is induced during multi-stage carcinogenesis in mouse skin and correlates with the metastatic potential of murine fibroblasts

✍ Scribed by Ann Marie Craig; G. Tim Bowden; Ann F. Chambers; Maureen A. Spearman; Amold H. Greenberg; Jim A. Wright; Marilyn McLeod; David T. Denhardt


Book ID
102865363
Publisher
John Wiley and Sons
Year
1990
Tongue
French
Weight
767 KB
Volume
46
Category
Article
ISSN
0020-7136

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✦ Synopsis


Secreted phosphoprotein I (SPP), also known as 2ar, osteopontin, 44-kDa bone phosphoprotein, bone sialoprotein I, and transformation-related phosphoprotein, is a 4 I .5-kDa glycosylated phosphoprotein secreted by many mammalian cell lines and expressed in a limited set of tissues. Using a cDNA probe, we found that SPP mRNA, which is barely detectable in normal mouse epidermis, was expressed at moderateto-high levels in 2 of 3 epidermal papillomas and at consistently high levels in 7 of 7 squamous-cell carcinomas induced by an initiation-promotion regimen. This contrasts with the transient induction we had previously observed after a single application of the tumor promoter I 2-Otetradecanoylphorbol-13-acetate (TPA). In a set of 5 independently isolated T24-H-ras-transfected mouse C3H lOTll2 cell lines, the levels of SPP mRNA correlated well with ras mRNA levels and with both experimental and spontaneous metastatic ability. SPP mRNA expression was also elevated in a derivative of mouse LTA cells transfected with genomic DNA from BI6FI melanoma cells and selected for increased experimental metastatic ability in the chick embryo. This apparent association of SPP expression with invasion, progression and metastasis, along with the presence of a functional ArgGlyAsp (RGD) cell adhesion site in SPP (osteopontin), leads us to propose that SPP may act as an autocrine adhesion factor for tumor cells.