Trophoblast glycoprotein, also known as TPBG, 5T4, Wnt-Activated Inhibitory Factor 1 or WAIF1, is a human protein encoded by a ''TPBG''
gene.
TPBG is an antagonist of
Wnt/β-catenin signalling pathway.
Clinical significance
5T4 is an
antigen expressed in a number of
carcinoma
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...
s.
It is an N-glycosylated transmembrane 72 kDa
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
containing eight
leucine-rich repeat
A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These tandem repeats common ...
s.
5T4 is often referred to as an ''oncofetal antigen'' due to its expression in
foetal trophoblast (where it was first discovered) or
trophoblast glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
(TPBG).
5T4 is found in
tumors including the
colorectal
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being ...
,
ovarian, and
gastric. Its expression is used as a prognostic aid in these cases. It has very limited expression in normal tissue but is widespread in
malignant tumours throughout their development. One study found that 5T4 was present in 85% of a cohort of 72 colorectal carcinomas and in 81% of a cohort of 27 gastric carcinomas.
Its confined expression appears to give 5T4 the potential to be a target for T cells in cancer
immunotherapy. There has been extensive research into its role in
antibody-directed immunotherapy through the use of the high-affinity
murine monoclonal antibody, mAb5T4, to deliver response modifiers (such as
staphylococcus aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...
superantigen
Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically it causes non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. SAgs are p ...
) accurately to a tumor.
5T4 is also the target of the
cancer vaccine
A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", ...
TroVax
TroVax is a cancer vaccine that was developed by Oxford BioMedica. No cancer vaccines have been proven to cure cancer or extend life yet, TroVax has been studied in a number of trials for colon cancer.
TroVax uses a tumor-associated antigen, 5T ...
which is in clinical trials for the treatment of a range of different
solid tumour types.
Interactions
TPBG has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
GIPC1.
References
Further reading
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Immunology
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