Osteopontin increases CD44 expression and cell adhesion in RAW 264.7 murine leukemia cells.
Journal Article (Journal Article)
BACKGROUND: Osteopontin (OPN) is an inducible cell attachment protein which binds alphavbeta3-integrin and CD44 receptors to promote tumor metastasis. We hypothesized that OPN alters expression of its CD44 receptor to promote neoplastic cell migration. METHODS: RAW264.7 cells were stimulated with OPN (0-10 nM) for 0-12 hours to determine the time- and concentration-dependence of CD44 protein and mRNA expression. In selected instances, a competitive ligand for the alphavbeta3-integrin, GRGDSP (50 nM), or an inhibitor of protein synthesis, anisomycin (10 microg/ml), was added. Cell adhesion to hyaluronan was assayed with the crystal violet assay. RESULTS: OPN upregulates plasma membrane total CD44 protein in a concentration-(ANOVA P = 0.001) and time-dependent (ANOVA P = 0.001) fashion. CD44v6 is not altered. Cell adhesion to hyaluronate increases in parallel with CD44 expression. Steady state mRNA levels for CD44 are not altered by OPN. 5 nM OPN increases CD44 protein half-life from 105 +/- 11 minutes to 278 +/- 15 minutes. (P < 0.03) Blockade of either alphavbeta3-integrin ablates the OPN-dependent increase in CD44. CONCLUSIONS: These data indicate that OPN increases plasma membrane CD44 expression and cell adhesion by binding to its alphavbeta3-integrin receptor. We conclude that OPN may promote tumor metastatic behavior by CD44 expression.
Full Text
Duke Authors
Cited Authors
- Marroquin, CE; Downey, L; Guo, H; Kuo, PC
Published Date
- August 15, 2004
Published In
Volume / Issue
- 95 / 1
Start / End Page
- 109 - 112
PubMed ID
- 15325806
International Standard Serial Number (ISSN)
- 0165-2478
Digital Object Identifier (DOI)
- 10.1016/j.imlet.2004.06.001
Language
- eng
Conference Location
- Netherlands