Disease relevance of TPBG

• 5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis [1].
• The monoclonal antibody 5T4 defines a human oncotrophoblast antigen expressed by a variety of carcinomas but with a restricted pattern of expression in normal adult tissues [2].
• The 5T4 antigen expression is strongly associated with metastasis in colorectal and gastric cancer, and, hence, the possible functions of the gene product and its relationship to tumor growth and progression are discussed [2].
• Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors [3].
• The monoclonal antibody 5T4, directed against a human tumor-associated antigen, was expressed as a secreted Fab superantigen fusion protein in Escherichia coli [4].

High impact information on TPBG

• The 5T4 antigen has been isolated from term placenta as a 72-kDa glycoprotein consisting of a 42-kDa core protein with extensive N-linked glycosylation [2].
• Northern analysis has demonstrated a major 2.5-kilobase mRNA present in cell lines serologically reactive with the monoclonal antibody 5T4 [2].
• Isolation of a cDNA encoding 5T4 oncofetal trophoblast glycoprotein. An antigen associated with metastasis contains leucine-rich repeats [2].
• Comparison of the 5T4 protein sequence with current sequence data bases has identified the presence of leucine-rich repeats, which are found in a variety of proteins from yeast, insects, and mammals [2].
• A cDNA has been isolated from a human placental library using pools of oligonucleotides based on amino acid sequence obtained from purified 5T4 molecules [2].

Chemical compound and disease context of TPBG

• The 5T4 oncofoetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia [5].

Biological context of TPBG

• 5T4 expression in A9 cells was also associated with an altered pattern of cell division, decreased cell-substratum adhesion and increased cellular motility [5].
• Transfection of full-length 5T4 cDNA into epithelial cells alters cell-cell contacts and cellular motility [6].
• Immunization of BALB/c and C57BL/6 mice with MVA-h5T4 and MVA-m5T4 constructs induced antibody responses to human and mouse 5T4, respectively [3].
• The human 5T4 oncotrophoblast leucine-rich glycoprotein may contribute to the process of placentation or metastasis by modulating cell adhesion, shape and motility [7].
• Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation [8].

Anatomical context of TPBG

• Furthermore, TIP-2/GIPC can be coimmunoprecipitated with 5T4 from HeLa cell lysates [1].
• These results support the hypothesis that 5T4 molecules may have a direct function in trophoblast and tumour cell invasion processes [5].
• Transmission and scanning electron microscopy showed that the 5T4 antigen is concentrated at microvillus projections of the plasma membrane both in the transfected A9 cells and in various carcinoma cell lines [5].
• Expression of 5T4 was found to be inversely related to the yield of tyrosine-hydroxylase (TH+)-expressing neurons in N2B27 medium, with additional mesoderm and endoderm transcript markers detected [8].
• We show that 5T4 antigen is transiently unregulated during HES4 and H1 human ES cell differentiation and its expression correlates with loss of the pluripotent markers OCT-4 and Tra-1-60 and upregulation of transcript markers associated with the three primary germ layers [8].

Associations of TPBG with chemical compounds

• A novel trophoblast cell surface antigen has been defined by a monoclonal antibody 5T4, raised following immunisation with wheat germ agglutinin (WGA) purified glycoproteins from deoxycholate (DOC) solubilised human syncytiotrophoblast plasma membrane (StMPM) [9].

Other interactions of TPBG

• Using a yeast two-hybrid approach, we describe a novel interaction between 5T4 and TIP-2/GIPC, a cytoplasmic interacting protein containing a PDZ domain [1].
• CD8 T-cell recognition of human 5T4 oncofetal antigen [10].

Analytical, diagnostic and therapeutic context of TPBG

• Confocal immunofluorescence microscopy revealed a 'polkadot' pattern of 5T4 antigen expression, heterogeneous in intensity between cells, but distributed over the entire cell surface [5].
• These data support the use of MVA-5T4 for tumor immunotherapy [3].
• Of 17 evaluable patients, 16 showed 5T4-specific cellular responses whereas 14 had detectable antibody levels following vaccination [11].
• Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFN gamma ELISPOT or ELISA [10].
• The purification of 5T4 antigenic molecules is described from term syncytiotrophoblast by a combination of lectin- and immunoaffinity chromatography and gel filtration giving up to 10,000-fold purification with 70% yield [12].

References