Fetuin, a New Globulin Isolated from Serum

Pedersen, Kai O.

doi:10.1038/154575a0

Cited by 284 publications

(110 citation statements)

References 2 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Fetuin-A is a liver secretory protein that accumulates in bone (24,25). Fetuin-A also appears to be expressed in bone, as transcripts have been detected in chondrocytes and osteoblasts (26).…”

Section: Discussionmentioning

confidence: 99%

Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer

Mintz¹,

Rietz

Cardó-Vila

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In response to an urgent need for improved diagnostic and predictive serum biomarkers for management of metastatic prostate cancer, we used phage display fingerprinting to analyze sequentially acquired serum samples from a patient with advancing prostate cancer. We identified a peptide ligand, CTFAGSSC, demonstrating an increased recovery frequency over time. Serum antibody reactivity to this peptide epitope increased in the index patient, in parallel with development of deteriorating symptoms. The antigen mimicking the peptide epitope was identified as alpha-2-HeremansSchmid glycoprotein, also known as fetuin-A. Metastatic prostate cancer cell lines and bone metastasis samples displayed robust fetuin-A expression, and we demonstrated serum immune reactivity to fetuin-A with concomitant development of metastatic castrateresistant disease in a large cohort of prostate cancer patients. Whereas fetuin-A is an established tumor antigen in several types of cancer, including breast cancer, glioblastoma, and pancreas cancer, this report is to our knowledge the first study implicating fetuin-A in prostate cancer and indicating that autoantibodies specific for fetuin-A show utility as a prognostic indicator for prostate cancer patients prone to progress to metastatic disease.cancer biomarker | peptide library | prostate cancer | phage display

show abstract

Section: Discussionmentioning

confidence: 99%

Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer

Mintz¹,

Rietz

Cardó-Vila

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…E. PIERCE The a globulin is of particular interest and is composed largely of a protein different from the albumin or serum globulins of the adult. This protein, fetuin, was first studied by Pedersen (1944Pedersen ( , 1945Pedersen ( , 1947 who showed that the molecular weight was only 48,700-50,600, which is less than that of the serum albumin (69,000; Scatchard, Batchelder & Brown, 1946), and that the iso-electric point was very low (pH 3-5;Pedersen, 1947). More recent investigations by Deutsch (1954) have confirmed these observations and have shown that fetuin is mucoprotein in nature.…”

mentioning

confidence: 99%

Electrophoretic and Immunological Studies on Sera from Calves from Birth to Weaning I. Electrophoretic Studies

Pierce

1955

J. Hyg.

View full text Add to dashboard Cite

Summary1. The serum proteins of calves from birth to weaning, and the maternal colostral whey have been examined with the ‘classical’ Tiselius electrophoresis apparatus. Differences were shown between calves fed colostrum and those partially deprived of colostrum.2. A study of the pre-colostral calf serum showed the presence of albumin and of two major components with mobilities similar to the α and β globulins of adult serum. A component forming approximately 1·4 % of the total serum proteins and with a mobility similar to that of γ1 or fibrinogen represented the γ1 globulin. This globulin component was not unconverted fibrinogen and may be autogenous γ globulin or γ globulin passively acquired in utero.3. Autogenous γ globulin was evident in colostrum-fed and colostrum-deprived calves shortly after birth. The γ1 and γ2 components could be distinguished by the 10th day after birth, at which time the γ1 globulin was the greater. By the 30th day the γ2 globulin exceeded the γ1 globulin and a smaller component termed the γ3 globulin could usually be detected between the γ2 and the salt boundary.4. Albumin concentrations generally fluctuated inversely to changes in the total serum globulins.5. The α globulins associated with fetuin declined shortly after birth in the colostrum-fed group. In the deprived group α globulin first rose and then fell. In both groups minimum α globulin values were reached at about the 30th day, when the α1 globulin, although initially the major component in pre-colostral calf serum, was more depleted than the α2.6. The β globulin frequently showed a transient though marked increase when the α globulins were at their lowest values.7. No changes in the electrophoretic mobilities of the major serum proteins were detected as the calves matured, and no significant difference was found between the mobilities of the electrophoretic components of calf and adult sera.8. The electrophoretic examination of colostral whey, colostral lacto-globulin fractions and calf serum immediately after suckling usually showed one lacto-globulin component. The relationship between the serum γ globulins and the lacto-globulin. is discussed.The author wishes to thank Dr M. Robertson, F.R.S., and Sir Alan Drury, F.R.S. for their interest and encouragement during the course of this work, Dr W. R. Kerr for his co-operation in supplying most of the serum and colostrum samples, and Dr A. W. Stableforth and Dr J. S. Paterson for making certain cattle available for these experiments.

show abstract

“…Bovine fetuin and the human homolog ␣2-HS-glycoprotein (AHSG) 1 are secreted by hepatocytes and constitute a major component of serum and the noncollagenous protein fraction of mineralized bone (1)(2)(3). Serum fetuin measured in cattle, sheep, and goats is highest in the 3rd trimester (i.e.…”

mentioning

confidence: 99%

Regulation of Osteogenesis by Fetuin

Binkert¹,

Demetriou²,

Sukhu³

et al. 1999

Journal of Biological Chemistry

118

View full text Add to dashboard Cite

Osteoporosis is a common problem of aging and results from a failure of homeostatic mechanisms to regulate osteogenesis and mineralization. Bovine and human forms of fetuin glycoprotein bind to the transforming growth factor (TGF)-␤/BMP (bone morphogenic protein) cytokines and block their osteogenic activity in cell culture assays (Demetriou, M., Binkert, C., Sukhu, B., Tenenbaum, H. C., and Dennis, J. W. (1996) J. Biol. Chem. 271, 12755-12761). Fetuin is a prominent serum glycoprotein and a major noncollagenous component of mineralized bone in mammals. In this study, we show that recombinant fetuin and native serum protein have similar potency as inhibitors of osteogenesis in dexamethasone-treated rat bone marrow cell cultures (dex-RBMC). Recombinant bovine fetuin also bound to TGF-␤1 and BMP-2 in vitro with kinetics similar to native fetuin. Although TGF-␤1 is required for osteogenesis in dex-RBMC, the cytokine also inhibited osteogenesis at concentrations >10 pM. Titration of fetuin or anti-TGF-␤1 antibodies into the bone marrow cultures in the presence of 10 pM TGF-␤1 restored osteogenesis, whereas titrations of the same reagents into cultures with 0.3 pM added TGF-␤1 were inhibitory, confirming the biphasic nature of the TGF-␤1 response. Suppression of osteogenesis by both TGF-␤1 and the antagonist proteins required their presence within the first 6 days of culture, well before mineralization at 10 -12 days. Northern analysis showed that both fetuin and high dose TGF-␤1 suppressed expression of the bone-associated transcripts alkaline phosphatase, osteopontin, collagen type I, and bone sialoprotein. The suppression of osteogenesis by fetuin and by high dose TGF-␤1 was accompanied by the differentiation of an alternate cell lineage with adipocyte characteristics. In summary, the biphasic osteogenic response to TGF-␤1 suggests that overlapping gradients of TGF-␤/BMP cytokines and fetuin regulate osteogenesis in remodeling bone.

show abstract

Fetuin, a New Globulin Isolated from Serum

Cited by 284 publications

References 2 publications

Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer

Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer

Electrophoretic and Immunological Studies on Sera from Calves from Birth to Weaning I. Electrophoretic Studies

Regulation of Osteogenesis by Fetuin

Contact Info

Product

Resources

About