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1,25-Dihydroxyvitamin D₃ Stimulates Synthesis and Secretion of Nonphosphorylated Osteopontin (Secreted Phosphoprotein 1) in Mouse JB6 Epidermal Cells¹

Department of Nutrition Sciences [P-L. C., C. W. P.] and Comprehensive Cancer Center [C. W. P.], University of Alabama at Birmingham, Birmingham, Alabama 35294

Murine JB6 epidermal cells can be irreversibly transformed into tumorigenic cells by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. One feature of this transformation is induction of the synthesis and secretion of the phosphoprotein osteopontin (also called secreted phosphoprotein 1 and previously referred to as transformation-related phosphoprotein, 2ar, bone sialoprotein 1, or M_r 44,000 bone phosphoprotein), an arginylglycylaspartic acid-containing cell adhesion glycoprotein the expression of which has been implicated in tumorigenesis and metastasis. Since 1,25-dihydroxyvitamin D₃, calcitriol, also transforms JB6 cells and, in other cell types, regulates osteopontin synthesis, we hypothesized that calcitriol-mediated transformation of JB6 cells would also cause induction of osteopontin synthesis and secretion.

Metabolic labeling with ³²PO₄ of near confluent JB6 cells (clone 41.5a) treated with calcitriol (0.1–100 ng/ml) for up to 48 h revealed only a minimal production of osteopontin, which is the major phosphoprotein secreted by 12-O-tetradecanoylphorbol-13-acetate-treated cells. Similar treatment followed by labeling with [³⁵S]methionine showed a substantial dose-dependent increase in the synthesis and secretion of osteopontin. This induction was not associated with increased cell proliferation or with cell transformation, as assayed by anchorage-independent growth. Calcitriol-treated cells were morphologically indistinguishable from control cells, while 12-O-tetradecanoylphorbol-13-acetate-treated cells acquired a distinctive morphology. No induction of osteopontin was found with 25-hydroxyvitamin D₃ or 24R,25-dihydroxyvitamin D₃.

These results show that calcitriol induces the synthesis and secretion of a nonphosphorylated form of osteopontin, in a cell type which normally makes little or none of this protein, and that the induction is not correlated with the tumorigenic transformation of these cells.

¹ This investigation was supported by NIH Grant DE06739 and a Research Career Development Award (K04 DE00247) to C. W. P. and a Clinical Nutrition Research Unit center grant (CA28103) from the National Cancer Institute to the Department of Nutrition Sciences (Dr. C. L. Krumdieck, P.I.).

² To whom requests for reprints should be addressed, at Department of Nutrition Sciences, University of Alabama at Birmingham, UAB Station, Birmingham, AL 35294.

Received 10/31/90. Accepted 2/ 6/91.

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