Fetuin-A ({alpha}2HS-glycoprotein) is a major serum adhesive protein that mediates growth signaling in breast tumor cells.
The identity of the cell adhesive factors in fetal bovine serum, commonly used to supplement growth media, remains a mystery due to the plethora of serum proteins. In the present analyses, we showed that fetuin-A, whose function in cellular attachment in tissue culture has been debated for many years, is indeed a major serum cell attachment factor particularly for tumor cells. We are able to report this because of a new purification strategy that has for the first time given us a homogeneous protein band in colloidal Coomassie-stained gels that retains biological activity. The tumor cells adhered to immobilized fetuin-A and not α(2)-macroglobulin, its major contaminant. The interaction of cells with fetuin-A was driven mainly by Ca(2+) ions, and cells growing in regular medium supplemented with fetal bovine serum were just as sensitive to loss of extracellular Ca(2+) ions as cells growing in fetuin-A. Fractionation of human serum revealed that cell attachment was confined to the fractions that had fetuin-A. Interestingly, the tumor cells also took up fetuin-A and secreted it back to the medium using an unknown mechanism that can be observed in live cells. The attachment of tumor cells to fetuin-A was accompanied by phosphatidylinositol 3-kinase/Akt activation that was down-regulated in cells that lack annexin-A6, one of the cell surface receptors for fetuin-A. Taken together, our data show the significance of fetuin-A in tumor cell growth mechanisms in vitro and open new research vistas for this protein.
Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Amos M
AM
Sakwe
Rainelli
R
Koumangoye
Shawn J
SJ
Goodwin
Josiah
J
Ochieng
D001798:Blood Proteins / Q000737:chemistry*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000737:chemistry; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005990:Glycerol / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006801:Humans; D007477:Ions; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D060749:alpha-2-HS-Glycoprotein; D000509:alpha-Fetoproteins / Q000737:chemistry*
C556354:AHSG protein, human; D001798:Blood Proteins; D007477:Ions; D060749:alpha-2-HS-Glycoprotein; D000509:alpha-Fetoproteins; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D005990:Glycerol; D002118:Calcium