Trophoblast glycoprotein, also known as TPBG, 5T4, Wnt-Activated Inhibitory Factor 1 or WAIF1, is a human protein encoded by a TPBGgene.[5] TPBG is an antagonist of Wnt/β-catenin signalling pathway.[6]
5T4 is found in tumors including the colorectal, 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.[8]
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 murinemonoclonal antibody, mAb5T4, to deliver response modifiers (such as staphylococcus aureussuperantigen) accurately to a tumor.
5T4 is also the target of the cancer vaccineTroVax which is in clinical trials for the treatment of a range of different solid tumour types.
^Starzynska T, Wiechowska-Kozlowska A, Marlicz K, Bromley M, Roberts SA, Lawniczak M, Kolodziej B, Zyluk A, Stern PL (Jun 1998). "5T4 oncofetal antigen in gastric carcinoma and its clinical significance". European Journal of Gastroenterology & Hepatology. 10 (6): 479–84. doi:10.1097/00042737-199806000-00008. PMID9855063. S2CID19687036.479-84&rft.date=1998-06&rft_id=https://api.semanticscholar.org/CorpusID:19687036#id-name=S2CID&rft_id=info:pmid/9855063&rft_id=info:doi/10.1097/00042737-199806000-00008&rft.aulast=Starzynska&rft.aufirst=T&rft.au=Wiechowska-Kozlowska, A&rft.au=Marlicz, K&rft.au=Bromley, M&rft.au=Roberts, SA&rft.au=Lawniczak, M&rft.au=Kolodziej, B&rft.au=Zyluk, A&rft.au=Stern, PL&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
^Starzynska T, Rahi V, Stern PL (Nov 1992). "The expression of 5T4 antigen in colorectal and gastric carcinoma". British Journal of Cancer. 66 (5): 867–9. doi:10.1038/bjc.1992.375. PMC1977963. PMID1419629.867-9&rft.date=1992-11&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977963#id-name=PMC&rft_id=info:pmid/1419629&rft_id=info:doi/10.1038/bjc.1992.375&rft.aulast=Starzynska&rft.aufirst=T&rft.au=Rahi, V&rft.au=Stern, PL&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977963&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
^Awan A, Lucic MR, Shaw DM, Sheppard F, Westwater C, Lyons SA, Stern PL (Jan 2002). "5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis". Biochemical and Biophysical Research Communications. 290 (3): 1030–6. doi:10.1006/bbrc.2001.6288. PMID11798178.1030-6&rft.date=2002-01&rft_id=info:doi/10.1006/bbrc.2001.6288&rft_id=info:pmid/11798178&rft.aulast=Awan&rft.aufirst=A&rft.au=Lucic, MR&rft.au=Shaw, DM&rft.au=Sheppard, F&rft.au=Westwater, C&rft.au=Lyons, SA&rft.au=Stern, PL&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
King KW, Sheppard FC, Westwater C, Stern PL, Myers KA (Jun 1999). "Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1445 (3): 257–70. doi:10.1016/s0167-4781(99)00055-x. PMID10366710.257-70&rft.date=1999-06&rft_id=info:doi/10.1016/s0167-4781(99)50055-x&rft_id=info:pmid/10366710&rft.aulast=King&rft.aufirst=KW&rft.au=Sheppard, FC&rft.au=Westwater, C&rft.au=Stern, PL&rft.au=Myers, KA&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
Awan A, Lucic MR, Shaw DM, Sheppard F, Westwater C, Lyons SA, Stern PL (Jan 2002). "5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis". Biochemical and Biophysical Research Communications. 290 (3): 1030–6. doi:10.1006/bbrc.2001.6288. PMID11798178.1030-6&rft.date=2002-01&rft_id=info:doi/10.1006/bbrc.2001.6288&rft_id=info:pmid/11798178&rft.aulast=Awan&rft.aufirst=A&rft.au=Lucic, MR&rft.au=Shaw, DM&rft.au=Sheppard, F&rft.au=Westwater, C&rft.au=Lyons, SA&rft.au=Stern, PL&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
Shaw DM, Woods AM, Myers KA, Westwater C, Rahi-Saund V, Davies MJ, Renouf DV, Hounsell EF, Stern PL (Apr 2002). "Glycosylation and epitope mapping of the 5T4 glycoprotein oncofoetal antigen". The Biochemical Journal. 363 (Pt 1): 137–45. doi:10.1042/0264-6021:3630137. PMC1222460. PMID11903056.137-45&rft.date=2002-04&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222460#id-name=PMC&rft_id=info:pmid/11903056&rft_id=info:doi/10.1042/0264-6021:3630137&rft.aulast=Shaw&rft.aufirst=DM&rft.au=Woods, AM&rft.au=Myers, KA&rft.au=Westwater, C&rft.au=Rahi-Saund, V&rft.au=Davies, MJ&rft.au=Renouf, DV&rft.au=Hounsell, EF&rft.au=Stern, PL&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222460&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
Mulryan K, Ryan MG, Myers KA, Shaw D, Wang W, Kingsman SM, Stern PL, Carroll MW (Oct 2002). "Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors". Molecular Cancer Therapeutics. 1 (12): 1129–37. PMID12481437.1129-37&rft.date=2002-10&rft_id=info:pmid/12481437&rft.aulast=Mulryan&rft.aufirst=K&rft.au=Ryan, MG&rft.au=Myers, KA&rft.au=Shaw, D&rft.au=Wang, W&rft.au=Kingsman, SM&rft.au=Stern, PL&rft.au=Carroll, MW&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID16303743.117-26&rft.date=2007&rft_id=info:doi/10.1093/dnares/12.2.117&rft_id=info:pmid/16303743&rft.aulast=Otsuki&rft.aufirst=T&rft.au=Ota, T&rft.au=Nishikawa, T&rft.au=Hayashi, K&rft.au=Suzuki, Y&rft.au=Yamamoto, J&rft.au=Wakamatsu, A&rft.au=Kimura, K&rft.au=Sakamoto, K&rft.au=Hatano, N&rft.au=Kawai, Y&rft.au=Ishii, S&rft.au=Saito, K&rft.au=Kojima, S&rft.au=Sugiyama, T&rft.au=Ono, T&rft.au=Okano, K&rft.au=Yoshikawa, Y&rft.au=Aotsuka, S&rft.au=Sasaki, N&rft.au=Hattori, A&rft.au=Okumura, K&rft.au=Nagai, K&rft.au=Sugano, S&rft.au=Isogai, T&rft_id=https://doi.org/10.1093%2Fdnares%2F12.2.117&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
Ward CM, Eastham AM, Stern PL (Jun 2006). "Cell surface 5T4 antigen is transiently upregulated during early human embryonic stem cell differentiation: effect of 5T4 phenotype on neural lineage formation". Experimental Cell Research. 312 (10): 1713–26. doi:10.1016/j.yexcr.2006.02.006. PMID16616918.1713-26&rft.date=2006-06&rft_id=info:doi/10.1016/j.yexcr.2006.02.006&rft_id=info:pmid/16616918&rft.aulast=Ward&rft.aufirst=CM&rft.au=Eastham, AM&rft.au=Stern, PL&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
Smyth LJ, Elkord E, Taher TE, Jiang HR, Burt DJ, Clayton A, van Veelen PA, de Ru A, Ossendorp F, Melief CJ, Drijfhout JW, Dermime S, Hawkins RE, Stern PL (Oct 2006). "CD8 T-cell recognition of human 5T4 oncofetal antigen". International Journal of Cancer. 119 (7): 1638–47. doi:10.1002/ijc.22018. PMID16646078. S2CID12989205.1638-47&rft.date=2006-10&rft_id=https://api.semanticscholar.org/CorpusID:12989205#id-name=S2CID&rft_id=info:pmid/16646078&rft_id=info:doi/10.1002/ijc.22018&rft.aulast=Smyth&rft.aufirst=LJ&rft.au=Elkord, E&rft.au=Taher, TE&rft.au=Jiang, HR&rft.au=Burt, DJ&rft.au=Clayton, A&rft.au=van Veelen, PA&rft.au=de Ru, A&rft.au=Ossendorp, F&rft.au=Melief, CJ&rft.au=Drijfhout, JW&rft.au=Dermime, S&rft.au=Hawkins, RE&rft.au=Stern, PL&rft_id=https://doi.org/10.1002%2Fijc.22018&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">
Okazaki S, Sekizawa A, Purwosunu Y, Farina A, Wibowo N, Okai T (Nov 2007). "Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women". Obstetrics and Gynecology. 110 (5): 1130–6. doi:10.1097/01.AOG.0000286761.11436.67. PMID17978129. S2CID24566450.1130-6&rft.date=2007-11&rft_id=https://api.semanticscholar.org/CorpusID:24566450#id-name=S2CID&rft_id=info:pmid/17978129&rft_id=info:doi/10.1097/01.AOG.0000286761.11436.67&rft.aulast=Okazaki&rft.aufirst=S&rft.au=Sekizawa, A&rft.au=Purwosunu, Y&rft.au=Farina, A&rft.au=Wibowo, N&rft.au=Okai, T&rfr_id=info:sid/en.wikipedia.org:TPBG" class="Z3988">