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Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; proposed identification of a widespread mucin as the tumor cell receptor

  • Review
  • Published:
Tumor Biology

Abstract

The identification of a tumor cell receptor for alpha-fetoprotein (AFP) has long been sought in the field of medicine. The uptake and endocytosis of AFP by rat tumor cells in 1983 sparked a series of confirmatory reports which were extended to include multiple tumor types in rats, mice, and humans. The following year, French investigators characterized the binding properties of the AFP receptor but they did not purify and characterize the receptor. It was not until 1991–1992 that an AFP receptor was partially purified and characterized from both human monocytes and breast cancer cells. By 1993, monoclonal antibodies had been raised against the “AFP receptor” derived from breast cancer extracts with claims that the receptor was a widespread oncoprotein biomarker for cancer. To date, that receptor has yet to be identified due to its complex multimeric structure and carbohydrate composition. The present report will review the literature of the multiple AFP receptors previously including their cellular uptake, transmembrane passage, and partial biochemical characterization. . In addition, evidence derived from computer modeling, proteolytic/fragmentation cleavage patterns, domain structure analysis, and protein binding software analysis will be presented in a proposed identification of a widespread protein/gene family of transmembrane proteins which fits many, if not most, of the criteria attributed to the AFP receptor. The proposed receptor protein family is tentatively identified as an epithelial cell surface mucin constituting one (or more) of many classes of single-pass transmembrane proteins. Present data do not support the concept that the AFP receptor is a “universal” tumor receptor and/or biomarker, but rather a widespread mucin protein that functions primarily in protecting and lubricating epithelial mucosal layers, and engaging in signal transduction; the mucin only binds AFP as a molecule serving in a subordinate or ancillary function.

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References

  1. Mizejewski GJ. Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp Biol Med Maywood. 2001;226:377–408.

    PubMed  CAS  Google Scholar 

  2. Mizejewski G. Mapping on structure-function peptide sites on the human alpha-fetoprotein amino acid sequence. Atlas of Genetics and Cytogenetics in Oncology and Haematology. Deep Insight Sect. 2009:1–65.

  3. Li MS, Li PF, He SP, Du GG, Li G. The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel 7402 cell line. World J Gastroenterol. 2002;8:469–75.

    PubMed  CAS  Google Scholar 

  4. Mizejewski GJ, MacColl R. Alpha-fetoprotein growth inhibitory peptides: potential leads for cancer therapeutics. Mol Cancer Ther. 2003;11:1243–55.

    Google Scholar 

  5. Li MS, Li PF, Yang FY, He SP, Du GG, Li G. The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells. Cell Res. 2002;12:151–6.

    Article  PubMed  Google Scholar 

  6. Mizejewski GJ. Review of the putative cell-surface receptors for alpha-fetoprotein identification of a candidate receptor protein family [Review]. Tumour Biol. 2011;32:241–58.

    Article  PubMed  CAS  Google Scholar 

  7. Laderoute MP, The characterization of a novel, widespread, PNA-reactive tumor associated antigen: The alpha-fetoprotein receptor/binding protein. Ph.D. Thesis, Faculty of Graduate Studies and Research, University of Alberta, Canada. 1991; pp. 1–256.

  8. Laderoute MP, Wilans D, Wegmann T, Longenecker M. The identification, isolation, and characterization of a 67-kilodalton, PNA-reactive autoantigen commonly expressed in human adenocarcinomas. Anticancer Res. 1994;14:1233–46.

    PubMed  CAS  Google Scholar 

  9. Moro R, Gulyaeva-Tcherkassova J, Stieber P. Increased alpha-fetoprotein receptor in the serum of patients with early-stage breast cancer. Curr Oncol. 2012;1:e1–8.

    Google Scholar 

  10. Tcherkassova J, Abramovich C, Moro R, Chen C, Schmit R, Gerber A, et al. Combination of CA125 and RECAF biomarkers for early detection of ovarian cancer. Tumour Biol. 2011;4:831–8.

    Article  CAS  Google Scholar 

  11. Moro R, Tamaoki T, Wegmann TG, Longnecker BM, Laderoute MP. Monoclonal antibodies directed against a widespread oncofetal antigen: the alpha-fetoprotem receptor. Tumor Biol. 1993;14:116–30.

    Article  CAS  Google Scholar 

  12. Kanevsky VY, Pozdnyakova LP, Aksenova OA, Severin SE, Karakov VY, Severin ES. Isolation and characterization of AFP-binding proteins from tumor and fetal tissues. Biochem Mol Biol Int. 1997;41:1143–51.

    PubMed  CAS  Google Scholar 

  13. Villacampa MJ, Moro R, Naval J, Failly-Crepin C, Lampreave F, Uriel J. Alpha-fetoprotein receptors in a human breast cancer cell line. Biochem Biophys Res Commun. 1984;122:1322–7.

    Article  PubMed  CAS  Google Scholar 

  14. Uriel J, Failly-Crepin C, Villacampa MJ, Pineiro A. Geuskens. Incorporation of AFP by the MCF-7 human breast cancer cell line. Tumor Biol. 1984;5:41–51.

    CAS  Google Scholar 

  15. Mizejewski GJ. Biological role of AFP in cancer: prospects for anticancer therapy. Expert Rev Anticancer Ther. 2002;6:89–115.

    Google Scholar 

  16. Benno RH, Williams TH. Evidence for intracellular localization of AFP in the developing rat brain. Brain Res. 1978;142:182–6.

    Article  PubMed  CAS  Google Scholar 

  17. Moro R, Uriel J. Early localization of AFP in the developing nervous system of the chicken. Oncodev Biol Med. 1981;2:391–9.

    PubMed  CAS  Google Scholar 

  18. Uriel J, Trojan J, Dubauch P, Pineira A. Intracellular AFP and albumin in the developing nervous system of the baboon. Pathol Biol. 1982;30:79–84.

    PubMed  CAS  Google Scholar 

  19. Toran-Alleran CD. Coexistence of α-fetoprotein, albumin and transferring immunoreactivity in neurons of the developing mouse brain. Nature. 1980;286:733–6.

    Article  Google Scholar 

  20. Trojan J, Uriel J. Immunocytochemical localization of AFP and serum albumin in ecto-, meso-, and endodermal tissue derivatives of the developing rat. Oncodev Biol Med. 1982;3:13–22.

    PubMed  CAS  Google Scholar 

  21. Uriel J, Poupon MF, Geuskens M. Alpha-fetoprotein uptake by cloned cell lines derived from a nickel-induced rat rhabdomysosarcoma. Br J Cancer. 1983;48:261–9.

    Article  PubMed  CAS  Google Scholar 

  22. Lorenzo HC, Geuskens M, Macho A, et al. Alpha-fetoprotein binding and uptake by primary cultures of human skeletal muscle. Tumor Biol. 1996;17:251–60.

    Article  CAS  Google Scholar 

  23. Geuskens M, Naval J, Uriel J. Ultra-structural studies of the intracellular translocation of endocytosed alpha-fetoprotein (AFP) by cytochemistry and of the uptake of 3H-arachidonic acid bound to AFP by autoradiography in rat rhabdomyosarcoma cells. J Cell Physiol. 1986;128:389–96.

    Article  PubMed  CAS  Google Scholar 

  24. Torres JM, Geuskens M, Uriel J. Receptor-mediated endocytosis and recycling of alpha-fetoprotein in human β-lymphoma and T-leukemia cells. Int J Cancer. 1991;47:110–7.

    Article  PubMed  CAS  Google Scholar 

  25. Li M, Li H, Li C, Guo L, Liu H, Zhou S, et al. Cytoplasmic alpha-fetoprotein functions as a co-repressor in RA-RAR signaling to promote the growth of human hepatoma Bel 7402 cells. Cancer Lett. 2009;285:190–9.

    Article  PubMed  CAS  Google Scholar 

  26. Laborda J, Naval J, Allouche M, Calvo M, Georgoulias V, Mishal Z, et al. Specific uptake of alpha-fetoprotein by malignant human lymphoid cells. Int J Cancer. 1987;40:314–8.

    Article  PubMed  CAS  Google Scholar 

  27. Naval J, Villacampa MJ, Goguel AF, Uriel J. Cell type specific receptors for AFP in a mouse T-lymphoma cell line. Proc Nat Acad Sci USA. 1985;82:3301–4.

    Article  PubMed  CAS  Google Scholar 

  28. Torres JM, Carracq N, Uriel J. Membrane proteins from lymphoblastoid cells showing cross-affinity for alpha-fetoprotein and albumin: isolation and characterization. Biochem Biophys Acta. 1992;1159:60–6.

    Article  PubMed  CAS  Google Scholar 

  29. Esteban C, Trojan J, Macho A, Mishal Z, Lafarge-Frayssinet C, Uriel J. Activation of an AFP/receptor pathway in human normal and malignant peripheral blood mononuclear cells. Leukemia. 1993;7:1807–16.

    PubMed  CAS  Google Scholar 

  30. Suzuki Y, Zeng CQY, Alpert E. Isolation and characterization of a specific alpha-fetoprotein receptor on human monocytes. J Clin Invest. 1992;9:1530–6.

    Article  Google Scholar 

  31. Alava MA, Sturralde M, Lampreave F, Pineiro A. Specific uptake of alpha-fetoprotein and albumin by rat Morris 777 hepatoma cells. Tum Biol. 1999;20:52–64.

    Article  CAS  Google Scholar 

  32. Wiseman G, Bramwell ME, Bhavanandan VP, Harris H. The structure of the CA-1 antigen. Biochem Soc Trans. 1984;12:537–8.

    PubMed  CAS  Google Scholar 

  33. Gupta RK, Morton DC. Immunochemical characterization of a fetal antigen isolated from spend medium of a human melanoma cell line. JNCI. 1983;70:993–1004.

    PubMed  CAS  Google Scholar 

  34. Sekine H, Ohno T, Kufe DW. Purification and characterization of a high molecular weight glycoprotein detectable in human milk and breast carcinomas. J Immunol. 1985;135:3610–5.

    PubMed  CAS  Google Scholar 

  35. Kufe D, Inghirami G, Abe M, et al. Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma. 1984;3:223–32.

    Article  PubMed  CAS  Google Scholar 

  36. Stanker LH, Vandelaan M, Juarez-Salinas H. One-step purification of mouse monoclonal antibodies from ascites fluid by hydroxylapatite chromatography. J Immun Methods. 1985;76:157–69.

    Article  CAS  Google Scholar 

  37. Nieuw Amerongen AV, Oderkerk CH, Veerman EC. Adsorption to hydroxyapatite of partially deglycosylated human salivary mucins in competition with phosvitin and phytate. Biol Chem Hoppe Seyler. 1991;8:585–91.

    Article  Google Scholar 

  38. Qiu SM, Wen G, Wen J, Soloway RD, Crowther RS. Interaction of human gallbladder mucin with calcium hydroxyapatite: binding studies and the effect on hydroxyapatite formation. Hepatology. 1995;21:1618–24.

    PubMed  CAS  Google Scholar 

  39. Chaturvedi P, Singh AP, Batra SK. Structure, evolution, and biology of the MUC4 mucin. FASEB J. 2008;22:966–81.

    Article  PubMed  CAS  Google Scholar 

  40. Seregni E, Botti C, Massaron S, Lombardo C, Capobianco A, Bogni A, et al. Structure, function and gene expression of epithelial mucins. Tumori. 1997;83:625–32.

    PubMed  CAS  Google Scholar 

  41. Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes. Mol Cancer. 2010; 9:118.

    Google Scholar 

  42. MUC6 apomucin shows a distinct normal tissue distribution that correlates with Lewis antigen expression in the human stomach. Gastroenterology. 1995; 109:723–734

  43. Rossi EA, McNeer RR, Price-Schiavi SA, Van den Brande JM, Komatsu M, Thompson JF, et al. Sialomucin complex, a heterodimeric glycoprotein complex. Expression as a soluble, secretable form in lactating mammary gland and colon. J Biol Chem. 1996;271:33476–85.

    Article  PubMed  CAS  Google Scholar 

  44. Packer LM, Williams SJ, Callaghan S, Gotley DC, McGuckin MA. Expression of the cell surface mucin gene family in adenocarcinomas. Int J Oncol. 2004;25:1119–26.

    PubMed  CAS  Google Scholar 

  45. Singh PK, Hollingsworth MA. Cell surface-associated mucins in signal transduction. Trends Cell Biol. 2006;16:467–76.

    Article  PubMed  CAS  Google Scholar 

  46. Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4:45–60.

    Article  PubMed  CAS  Google Scholar 

  47. Carraway KL, Hull SR. O-glycosylation pathway for mucin-type glycoproteins. Bioessays. 1989;10:117–21.

    Article  PubMed  CAS  Google Scholar 

  48. Carraway KL, Price-Schiavi SA, Komatsu M, Jepson S, Perez A, Carraway CA. Muc4/sialomucin complex in the mammary gland and breast cancer. J Mammary Gland Biol Neoplasia. 2001;6:323–37.

    Article  PubMed  CAS  Google Scholar 

  49. Nollet S, Moniaux N, Maury J, Petitprez D, Degand P, Laine A, et al. Human mucin gene MUC4: organization of its 5'-region and polymorphism of its central tandem repeat array. Biochem J. 1998;332(Pt 3):739–48.

    PubMed  CAS  Google Scholar 

  50. Moniaux N, Nollet S, Porchet N, Degand P, Laine A, Aubert JP. Complete sequence of the human mucin MUC4: a putative cell membrane-associated mucin. Biochem J. 1999;338(Pt 2):325–33.

    Article  PubMed  CAS  Google Scholar 

  51. Carraway KL, Ramsauer VP, Carraway CA. Glycoprotein contributions to mammary gland and mammary tumor structure and function: roles of adherens junctions, ErbBs and membrane MUCs. J Cell Biochem. 2005;96:914–26.

    Article  PubMed  CAS  Google Scholar 

  52. Zalewska A, Zwierz K, Zółkowski K, Gindzieński A. Structure and biosynthesis of human salivary mucins. Acta Biochim Pol. 2000;47:1067–79.

    PubMed  CAS  Google Scholar 

  53. Mall AS, McLeod HA, Hickman R, Kahn D, Dent DM. Fragmentation pattern of mucins in normal and diseased gastric mucosae: a glycoprotein fractionates with gastric mucins purified from mucosal scrapings of cancer and peptic ulcer patients. Digestion. 1999;60:216–26.

    Article  PubMed  CAS  Google Scholar 

  54. Cao R, Wang TT, DeMaria G, Sheehan JK, Kesimer M. Mapping the protein domain structures of the respiratory mucins: a mucin proteome coverage study. J Proteome Res. 2012;11:4013–4023v.

    Article  PubMed  CAS  Google Scholar 

  55. List SJ, Findlay BP, Forstner GG, Forstner JF. Enhancement of the viscosity of mucin by serum albumin. Biochem J. 1978;175:565–71.

    PubMed  CAS  Google Scholar 

  56. Mukhopadhyay P, Chakraborty S, Ponnusamy MP, Lakshmanan I, Jain M, Batra SK. Mucins in the pathogenesis of breast cancer: implications in diagnosis, prognosis and therapy. Biochim Biophys Acta. 2011;1815:224–40.

    PubMed  CAS  Google Scholar 

  57. Pratt WS, Crawley S, Hicks J, Ho J, Nash M, Kim YS, et al. Multiple transcripts of MUC3: evidence for two genes, MUC3A and MUC3B. Biochem Biophys Res Commun. 2000;275:916–23.

    Article  PubMed  CAS  Google Scholar 

  58. Senapati S, Gnanapragassam VS, Moniaux N, Momi N, Batra SK. Role of MUC4-NIDO domain in the MUC4-mediated metastasis of pancreatic cancer cells. Oncogene. 2012;31:3346–56.

    Article  PubMed  CAS  Google Scholar 

  59. Williams SJ, Munster DJ, Quin RJ, Gotley DC, McGuckin MA. The MUC3 gene encodes a transmembrane mucin and is alternatively spliced. Biochem Biophys Res Commun. 1999;261(1):83–9.

    Article  PubMed  CAS  Google Scholar 

  60. Hijikata M, Matsushita I, Tanaka G, Tsuchiya T, Ito H, Tokunaga K, et al. Molecular cloning of two novel mucin-like genes in the disease-susceptibility locus for diffuse panbronchiolitis. Hum Genet. 2011;129(2):117–28.

    Article  PubMed  CAS  Google Scholar 

  61. Ho SB, Luu Y, Shekels LL, Batra SK, Kandarian B, Evans DB, et al. Activity of recombinant cysteine-rich domain proteins derived from the membrane-bound MUC17/Muc3 family mucins. Biochim Biophys Acta. 2010;1800:629–38.

    Article  PubMed  CAS  Google Scholar 

  62. Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer. 2009;9:874–85.

    Article  PubMed  CAS  Google Scholar 

  63. Singh AP, Chaturvedi P, Batra SK. Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy. Cancer Res. 2007;67:433–6.

    Article  PubMed  CAS  Google Scholar 

  64. Desseyn JL, Clavereau I, Laine A. Cloning, chromosomal localization and characterization of the murine mucin gene orthologous to human MUC4. Eur J Biochem. 2002;269:3150–9.

    Article  PubMed  CAS  Google Scholar 

  65. Carraway KL, Perez A, Idris N, Jepson S, Arango M, Komatsu M, et al. Muc4/sialomucin complex, the intramembrane ErbB2 ligand, in cancer and epithelia: to protect and to survive. Prog Nucleic Acid Res Mol Biol. 2002;71:149–85.

    Article  PubMed  CAS  Google Scholar 

  66. Yonezawa S, Goto M, Yamada N, Higashi M, Nomoto M. Expression profiles of MUC1, MUC2, and MUC4 mucins in human neoplasms and their relationship with biological behavior. Proteomics. 2008;8:3329–41.

    Article  PubMed  CAS  Google Scholar 

  67. Workman HC, Sweeney C, Carraway 3rd KL. The membrane mucin Muc4 inhibits apoptosis induced by multiple insults via ErbB2-dependent and ErbB2-independent mechanisms. Cancer Res. 2009;69:2845–52.

    Article  PubMed  CAS  Google Scholar 

  68. Carraway 3rd KL, Funes M, Workman HC, Sweeney C. Contribution of membrane mucins to tumor progression through modulation of cellular growth signaling pathways. Curr Top Dev Biol. 2007;78:1–22.

    Article  PubMed  CAS  Google Scholar 

  69. Chen AC, Migliaccio I, Rimawi M, Lopez-Tarruella S, Creighton CJ, Massarweh S, et al. Upregulation of mucin4 in ER-positive/HER2-overexpressing breast cancer xenografts with acquired resistance to endocrine and HER2-targeted therapies. Breast Cancer Res Treat. 2012;134:583–93.

    Article  PubMed  CAS  Google Scholar 

  70. Jain M, Venkatraman G, Moniaux N, Kaur S, Kumar S, Chakraborty S, et al. Monoclonal antibodies recognizing the non-tandem repeat regions of the human mucin MUC4 in pancreatic cancer. PLoS One. 2011;8:23344.

    Article  CAS  Google Scholar 

  71. Chaturvedi P, Singh AP, Chakraborty S, Chauhan SC, Bafna S, Meza JL, et al. MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. Cancer Res. 2008;68:2065–70.

    Article  PubMed  CAS  Google Scholar 

  72. Gipson IK, Spurr-Michaud S, Moccia R, Zhan Q, Toribara N, Ho SB, et al. MUC4 and MUC5B transcripts are the prevalent mucin messenger ribonucleic acids of the human endocervix. Biol Reprod. 1999;60:58–64.

    Article  PubMed  CAS  Google Scholar 

  73. Alameda F, Mejías-Luque R, Garrido M, de Bolós C. Mucin genes (MUC2, MUC4, MUC5AC, and MUC6) detection in normal and pathological endometrial tissues. Int J Gynecol Pathol. 2007;26:61–5.

    Article  PubMed  Google Scholar 

  74. Mao TL, Kurman RJ, Huang CC, Lin MC, Shih IM. Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis. Am J Surg Pathol. 2007;31:1726–32.

    Article  PubMed  Google Scholar 

  75. Newby D, Dalgliesh G, Lyall F, Aitken DA. Alphafetoprotein and alphafetoprotein receptor expression in the normal human placenta at term. Placenta. 2005;26:190–200.

    Article  PubMed  CAS  Google Scholar 

  76. Buisine MP, Devisme L, Savidge TC, Gespach C, Gosselin B, Porchet N, et al. Mucin gene expression in human embryonic and fetal intestine. Gut. 1998;43:519–24.

    Article  PubMed  CAS  Google Scholar 

  77. Buisine MP, Devisme L, Maunoury V, Deschodt E, Gosselin B, Copin MC, et al. Developmental mucin gene expression in the gastroduodenal tract and accessory digestive glands. I. Stomach. A relationship to gastric carcinoma. J Histochem Cytochem. 2000;48:1657–66.

    Article  PubMed  CAS  Google Scholar 

  78. Komatsu M, Arango ME, Carraway KL. Synthesis and secretion of Muc4/sialomucin complex: implication of intracellular proteolysis. Biochem J. 2002;368(Pt 1):41–8.

    Article  PubMed  CAS  Google Scholar 

  79. Escande F, Lemaitre L, Moniaux N, Batra SK, Aubert JP, Buisine MP. Genomic organization of MUC4 mucin gene. Towards the characterization of splice variants. Eur J Biochem. 2002;269:3637–44.

    Article  PubMed  CAS  Google Scholar 

  80. Stern DF, Heffernan PA, Weinberg RA. p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. Mol Cell Biol. 1986;6:1729–40.

    PubMed  CAS  Google Scholar 

  81. Jepson S, Komatsu M, Haq B, Arango ME, Huang D, Carraway CA, et al. Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Oncogene. 2002;24:7524–32.

    Article  CAS  Google Scholar 

  82. Wu K, Salas PJ, Yee L, Fregien N, Carraway KL. Tissue and tumor expression of a cell surface glycoprotein complex containing an integral membrane glycoprotein activator of p185neu. Oncogene. 1994;9:3139–47.

    PubMed  CAS  Google Scholar 

  83. Rakha EA, Boyce RW, Abd El-Rehim D, Kurien T, Green AR, Paish EC, et al. Expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and their prognostic significance in human breast cancer. Mod Pathol. 2005;18:1295–304.

    Article  PubMed  CAS  Google Scholar 

  84. Funes M, Miller JK, Lai C, Carraway 3rd KL, Sweeney C. The mucin Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3. J Biol Chem. 2006;281:19310–9.

    Article  PubMed  CAS  Google Scholar 

  85. Ponnusamy MP, Seshacharyulu P, Vaz A, Dey P, Batra SK. MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells. J Ovarian Res. 2011;4:7–10.

    Article  PubMed  CAS  Google Scholar 

  86. Mizejewski GJ. Mechanism of cancer growth suppression of alpha-fetoprotein derived growth inhibitory peptides (GIP): comparison of GIP-34 versus GIP-8 (AFPep). Updates and prospects. Cancers. 2011;3:2709–33.

    Article  CAS  Google Scholar 

  87. Botti C, Seregni E, Ménard S, Collini P, Tagliabue E, Campiglio M, et al. Two novel monoclonal antibodies against the MUC4 tandem repeat reacting with an antigen overexpressed by lung cancer. Int J Biol Markers. 2000;15:312–20.

    PubMed  CAS  Google Scholar 

  88. Moniaux N, Varshney GC, Chauhan SC, Copin MC, Jain M, Wittel UA, et al. Generation and characterization of anti-MUC4 monoclonal antibodies reactive with normal and cancer cells in humans. J Histochem Cytochem. 2004;52:253–61.

    Article  PubMed  CAS  Google Scholar 

  89. Bafna S, Singh AP, Moniaux N, Eudy JD, Meza JL, Batra SK. MUC4, a multifunctional transmembrane glycoprotein, induces oncogenic transformation of NIH3T3 mouse fibroblast cells. Cancer Res. 2008;68:9231–8.

    Article  PubMed  CAS  Google Scholar 

  90. Doi M, Yokoyama A, Kondo K, Ohnishi H, Ishikawa N, Hattori N, et al. Anti-tumor effect of the anti-KL-6/MUC1 monoclonal antibody through exposure of surface molecules by MUC1 capping. Cancer Science. 2006;97:420–9.

    Article  PubMed  CAS  Google Scholar 

  91. Komatsu M, Yee L, Carraway KL. Overexpression of sialomucin complex, a rat homologue of MUC4, inhibits tumor killing by lymphokine-activated killer cells. Cancer Res. 1999;59:2229–36.

    PubMed  CAS  Google Scholar 

  92. Yonezawa S, Higashi M, Yamada N, Yokoyama S, Kitamoto S, Kitajima S, et al. Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. Pathol Int. 2011;61:697–716.

    Article  PubMed  CAS  Google Scholar 

  93. Segal-Eiras A, Croce MV. Breast cancer associated mucin: a review. Allergol Immunopathol (Madr). 1997;25:176–81.

    CAS  Google Scholar 

  94. Mizejewski GJ, Mirowski M, Garnuszek P, Maurin M, Cohen BD, Poiesz BJ, et al. Targeted delivery of anti-cancer growth inhibitory peptides derived from human alpha-fetoprotein: review of an International Multi-Center Collaborative Study. J Drug Target. 2010;18:575–88.

    Article  PubMed  CAS  Google Scholar 

  95. Li M, Zhou S, Liu X, Li P, McNutt MA, Li G. Alpha-fetoprotein shields hepatocellular carcinoma cells from apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand. Cancer Lett. 2007;249:227–34.

    Article  PubMed  CAS  Google Scholar 

  96. Li M, Liu X, Zhou S, Li P, Li G. Effects of alpha fetoprotein on escape of Bel 7402 cells from attack of lymphocytes. BMC Cancer. 2005;5:96–2001.

    Article  PubMed  CAS  Google Scholar 

  97. Uriel J, Naval J, Laborda J. Alpha-fetoprotein mediated transfer of arachidonic acid into cultured cloned cells derived from a rat rhabdomyosarcoma. J Biol Chem. 1987;262:2579–3585.

    Google Scholar 

  98. Line BR, Feustel PJ, Festin SM, Andersen TT, Dansereau RN, Lukasiewicz RL, et al. Scintigraphic detection of breast cancer xenografts with Tc-99m natural and recombinant human alpha-fetoprotein. Cancer Biother Radiopharm. 1999;6:485–94.

    Article  Google Scholar 

  99. Biddle W, Sarcione EJ. Specific cytoplasmic alpha-fetoprotein binding protein in MCF-7 human breast cancer cells and primary breast cancer tissue. Breast Cancer Res Treat. 1987;10:279–86.

    Article  PubMed  CAS  Google Scholar 

  100. Mirowski M, S'Witalska J, Wiercioch R, Byszewska E, Niewiadomska H, Michalska M. Uptake of radiolabelled alpha-fetoprotein by experimental mammary adenocarcinoma and adenoma: in vivo and in vitro studies. Nucl Med Commun. 2003;3:297–303.

    Article  Google Scholar 

  101. Moro R, Villacampa MJ. Short sequences of high homology between the primary structures of alpha-fetoprotein and albumin. Tumour Biol. 1986;7:115–21.

    PubMed  CAS  Google Scholar 

  102. Posypanova GA, Gorokhovets NV, Makarov VA, Savvateeva LV, Kireeva NN, Severin SE, et al. Recombinant alpha-fetoprotein C-terminal fragment: the new recombinant vector for targeted delivery. J Drug Target. 2008;16:321–8.

    Article  PubMed  CAS  Google Scholar 

  103. Moro R. The AFP receptor—a widespread oncofetal antigen. In: Mizejewski GJ, Jacobson HI, editors. Biological activities of alpha-fetoprotein, vol. II. Boca Raton: CRC Press; 1989. p. 120–6.

    Google Scholar 

  104. Line BR, Epstein MD, Mizejewski GJ. Medicinal potential of AFP as a tumor imaging agent. In: Mizejewski GJ, Jacobson HI, editors. Biological activities of alpha fetoprotein, vol. II. Boca Raton: CRC Press; 1989. p. 139–48.

    Google Scholar 

  105. Hajeri-Germond M, Naval J, Trojan J, Uriel J. The uptake of alpha-fetoprotein by C-1300 mouse neuroblastoma cells. Br J Cancer. 1985;51:791–7.

    Article  PubMed  CAS  Google Scholar 

  106. Mizejewski GJ. Alpha-fetoprotein as a biologic response modifier; relevance to domain and subdomain structure. Proc Soc Exp Biol Med. 1997;215:333–62.

    PubMed  CAS  Google Scholar 

  107. Moro R, Hueguerot C, Vercelli-Retta J, Fielitz W, Lopez JJ, Roca R. The use of radioiodinated alpha-fetoprotein for the scintigraphic detection of mouse mammary carcinomas. Nucl Med Commun. 1984;5:5–12.

    Article  PubMed  CAS  Google Scholar 

  108. Mizejewski GJ. Phylogenyof alpha-fetoprotein in vertebrates: survey of biochemical and physiological data; critical reviews eukaryotic. Gene Expr. 1995;5:281–316.

    CAS  Google Scholar 

  109. Dauphinee MJ, Mizejewski GJ. Human alpha-fetoprotein contains potential heterodimerization motifs capable of interaction with nuclear receptors and transcription/growth factors. Med Hypothesis. 2002;22:2817–21.

    Google Scholar 

  110. Mizejewski GJ, Smith G, Butterstein G. Review and proposed action of alpha-fetoprotein growth inhibitory peptides as estrogen and cytoskeleton-associated factors. Cell Biol Int. 2004;28:9103–33.

    Article  CAS  Google Scholar 

  111. Lutsenko SV, Feldman NB, Finakova GV, Gukasova NV, Petukhov SP, Posypanova GA, et al. Antitumor activity of alpha-fetoprotein and epidermal growth factor conjugates in vitro and in vivo. Tumor Biol. 2000;21:367–74.

    Article  CAS  Google Scholar 

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Acknowledgments

The author expresses his thanks and gratitude to Ms. Jennifer Wright for her time comitant and expenditure in the typing and processing of this manscript. Thanks is also extended to Ms. Rachel Moseley and Mr.Christopher Harkins for the computer graphics artwork and illustrations presented here. Acknowldgement is also made to Serometrix Biotech, LLC, Sytracuse, NY, for the use of their proprietary protein-to-protein binding site computer software (see www.serometrix.com).

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  1. Wadsworth Center, Division of Translational Medicine, New York State Department of Health, Empire State Plaza, Albany, NY, 12201, USA

    G. J. Mizejewski

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  1. G. J. Mizejewski
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Correspondence to G. J. Mizejewski.

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Mizejewski, G.J. Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; proposed identification of a widespread mucin as the tumor cell receptor. Tumor Biol. 34, 1317–1336 (2013). https://doi.org/10.1007/s13277-013-0704-4

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  • DOI: https://doi.org/10.1007/s13277-013-0704-4

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