Document Detail

Fetuin-A ({alpha}2HS-glycoprotein) is a major serum adhesive protein that mediates growth signaling in breast tumor cells.
MedLine Citation:
PMID:  20956534     Owner:  NLM     Status:  MEDLINE    
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.
Amos M Sakwe; Rainelli Koumangoye; Shawn J Goodwin; Josiah Ochieng
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-18
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-27     Completed Date:  2011-02-09     Revised Date:  2014-05-29    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  41827-35     Citation Subset:  IM    
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MeSH Terms
Blood Proteins / chemistry*
Breast Neoplasms / metabolism,  pathology*
Calcium / chemistry
Cell Adhesion
Cell Membrane / metabolism
Cell Proliferation
Gene Expression Regulation, Neoplastic*
Glycerol / chemistry
Green Fluorescent Proteins / chemistry
MAP Kinase Signaling System
Phosphatidylinositol 3-Kinases / metabolism
Signal Transduction*
alpha-Fetoproteins / chemistry*
Grant Support
Reg. No./Substance:
0/AHSG protein, human; 0/Blood Proteins; 0/Ions; 0/alpha-2-HS-Glycoprotein; 0/alpha-Fetoproteins; 147336-22-9/Green Fluorescent Proteins; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; PDC6A3C0OX/Glycerol; SY7Q814VUP/Calcium

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