Interactions of alpha2-HS-glycoprotein (fetuin) with MMP-3 and murine squamous cell carcinoma cells.
Alpha2-HS glycoprotein (fetuin) is a major plasma glycoprotein predominantly synthesized by the liver. We have previously demonstrated that human fetuin produced by hepatocellular carcinoma cells can activate the matrix metalloproteinase MMP-9 (gelatinase-B). Stromelysin-1 (MMP-3) is over-expressed in murine skin tumors and is associated with a metastatic cell phenotype. We hypothesize that fetuin plays a role in tumor progression of cell types which by themselves do not have the ability to express fetuin. Immunohistochemical staining revealed that fetuin surrounds the tumor cells in murine squamous cell carcinoma tumor specimens, similar to the expression pattern previously seen for MMP-3. The physical association of fetuin and MMP-3 was demonstrated by immunoprecipitation of radiolabeled fetuin by antibodies to MMP-3. Fetuin facilitates the conversion of pro-MMP-3 to its active form, although this effect is indirect. The association of iodinated fetuin to the cell surface of intact cultured cells derived from a murine tumor with squamous (B9) and spindle (A5) morphologies was determined by binding experiments and Scatchard analysis. Fetuin binds with Bmax values in the range of 1.26-2.1 (mean = 1.7) fmol/1 x 10(5) cells for A5 cells, and 1.5-1.7 (mean = 1.6) fmol/1 x 10(5) cells for B9 cells. The mean KD was 0.46+/-0.19 nmol for both A5 and B9 cells. Our data therefore are consistent with the model that fetuin binds to the cell surface of tumor cells and acts to localize and anchor other molecules important during tumor progression to the plasma membrane.
Leite-Browning
Maria L
ML
Department of Biochemistry, Meharry Medical College, 1005 D.B. Todd Boulevard, Nashville, TN 37208, USA.
McCawley
Lisa J
LJ
Choi
Oksoon H
OH
Matrisian
Lynn M
LM
Ochieng
Josiah
J
D000818:Animals; D016466:CHO Cells; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000378:metabolism; D006224:Cricetinae; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000502:physiology*; D051379:Mice; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000032:analysis / Q000502:physiology*
D000509:alpha-Fetoproteins; D019278:Matrix Metalloproteinase 3