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Cellular and Molecular Life Sciences

, Volume 72, Issue 23, pp 4475–4500 | Cite as

MUC1 (CD227): a multi-tasked molecule

  • Vasso Apostolopoulos
  • Lily Stojanovska
  • Sharron E. Gargosky
Review

Abstract

Mucin 1 (MUC1 [CD227]) is a high-molecular weight (>400 kDa), type I membrane-tethered glycoprotein that is expressed on epithelial cells and extends far above the glycocalyx. MUC1 is overexpressed and aberrantly glycosylated in adenocarcinomas and in hematological malignancies. As a result, MUC1 has been a target for tumor immunotherapeutic studies in mice and in humans. MUC1 has been shown to have anti-adhesive and immunosuppressive properties, protects against infections, and is involved in the oncogenic process as well as in cell signaling. In addition, MUC1 plays a key role in the reproductive tract, in the immune system (affecting dendritic cells, monocytes, T cells, and B cells), and in chronic inflammatory diseases. Evidence for all of these roles for MUC1 is discussed herein and demonstrates that MUC1 is truly a multitasked molecule.

Keywords

MUC1 CD227 PEM EMA MUC1 isoforms MUC1 expression MUC1 structure MUC1 and disease MUC1 and pathogens MUC1 and cancer 

Abbreviations

AGR2

Anterior gradient 2

ALK

Anaplastic lymphoma kinase

C. jejeni

Campylobacter jejeni

CA

Cancer antigen

CASA

Cancer-associated serum antigen

CD

Cluster of differentiation

CEA

Carcinoembryonic antigen

CTL

Cytotoxic T lymphocyte

DC

Dendritic cell

EGFR

Epidermal growth factor receptor

FGF

Fibroblast growth factor

GalNac

N-acetyl galactosamine

GlcNAc

N-acetyl glucosamine

H. pylori

Helicobacter pylori

HLA

Human leukocyte antigen

HMFG

Human milk fat globule

Hsp

Heat shock protein

IBD

Inflammatory bowel disease

ICAM-1

Intercellular adhesion molecule 1

IFN

Interferon

IL

Interleukin

Mab

Monoclonal antibody

MAG

Myelin-associated glycoprotein

MALT

Mucosa-associated lymphoid tissue

MAV-1

Murine adenovirus type 1

MCA

Mucin-like carcinoma-associated antigen

MDSC

Myeloid-derived suppressor cell

MGL

Macrophage galactose lectin

MHC

Major histocompatibility complex

MSA

Mammary serum antigen

MUC1

Human mucin 1

Muc1

Other species mucin 1

NK

Natural killer

NMR

Nuclear magnetic resonance

OSA

Ovarian serum antigen

P. aeruginosa

Pseudomonas aeruginosa

RSV

Respiratory syncytial virus

SEA

Sea urchin sperm protein-enterokinase-agrin

siRNA

Small interfering RNA

TF or T

Thomsen-Friedenreich

TGF

Transforming growth factor

Th

T helper

TLR

Toll-like receptor

TNF

Tumor necrosis factor

Tn

Monosaccharide of TF

STn

Sialylated Tn

VEGF

Vascular endothelial growth factor

VNTR

Variable number of tandem repeats

Notes

Acknowledgments

The authors would like to thank Prima Biomed Ltd. for their helpful discussions.

References

  1. 1.
    Apostolopoulos V, McKenzie IF (1994) Cellular mucins: targets for immunotherapy. Crit Rev Immunol 14:293–309PubMedCrossRefGoogle Scholar
  2. 2.
    Arklie J, Taylor-Papadimitrious J, Bodmer W, Egan M, Millis R (1981) Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers. Int J Cancer 28:23–29PubMedCrossRefGoogle Scholar
  3. 3.
    Swallow DM, Griffiths B, Bramwell M, Wiseman G, Burchell J (1986) Detection of the urinary ‘PUM’ polymorphism by the tumour-binding monoclonal antibodies Ca1, Ca2, Ca3, HMFG1, and HMFG2. Dis Markers 4:247–254PubMedGoogle Scholar
  4. 4.
    Taylor-Papadimitriou J, Peterson JA, Arklie J, Burchell J, Ceriani RL, Bodmer WF (1981) Monoclonal antibodies to epithelium-specific components of the human milk fat globule membrane: production and reaction with cells in culture. Int J Cancer 28:17–21PubMedCrossRefGoogle Scholar
  5. 5.
    Burchell J, Gendler S, Taylor-Papadimitriou J, Girling A, Lewis A, Millis R, Lamport D (1987) Development and characterization of breast cancer reactive monoclonal antibodies directed to the core protein of the human milk mucin. Cancer Res 47:5476–5482PubMedGoogle Scholar
  6. 6.
    Hilkens J, Buijs F, Hilgers J, Hageman P, Calafat J, Sonnenberg A, van der Valk M (1984) Monoclonal antibodies against human milk-fat globule membranes detecting differentiation antigens of the mammary gland and its tumors. Int J Cancer 34:197–206PubMedCrossRefGoogle Scholar
  7. 7.
    Magnani JL, Steplewski Z, Koprowski H, Ginsburg V (1983) Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. Cancer Res 43:5489–5492PubMedGoogle Scholar
  8. 8.
    Gendler SJ, Burchell JM, Duhig T, Lamport D, White R, Parker M, Taylor-Papadimitriou J (1987) Cloning of partial cDNA encoding differentiation and tumor-associated mucin glycoproteins expressed by human mammary epithelium. Proc Natl Acad Sci 84:6060–6064PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Gendler SJ, Lancaster CA, Taylor-Papadimitriou J, Duhig T, Peat N, Burchell J, Pemberton L, Lalani EN, Wilson D (1990) Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. J Biol Chem 265:15286–15293PubMedGoogle Scholar
  10. 10.
    Lan MS, Batra SK, Qi WN, Metzgar RS, Hollingsworth MA (1990) Cloning and sequencing of a human pancreatic tumor mucin cDNA. J Biol Chem 265:15294–15299PubMedGoogle Scholar
  11. 11.
    Ligtenberg MJ, Vos HL, Gennissen AM, Hilkens J (1990) Episialin, a carcinoma-associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini. J Biol Chem 265:5573–5578PubMedGoogle Scholar
  12. 12.
    Siddiqui J, Abe M, Hayes D, Shani E, Yunis E, Kufe D (1988) Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen. Proc Natl Acad Sci 85:2320–2323PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Wreschner DH, Hareuveni M, Tsarfaty I, Smorodinsky N, Horev J, Zaretsky J, Kotkes P, Weiss M, Lathe R, Dion A et al (1990) Human epithelial tumor antigen cDNA sequences. Differential splicing may generate multiple protein forms. Eur J Biochem 189:463–473PubMedCrossRefGoogle Scholar
  14. 14.
    Gendler SJ, Spicer AP, Lalani EN, Duhig T, Peat N, Burchell J, Pemberton L, Boshell M, Taylor-Papadimitriou J (1991) Structure and biology of a carcinoma-associated mucin, MUC1. Am Rev Respir Dis 144:S42–S47PubMedCrossRefGoogle Scholar
  15. 15.
    Hilkens J, Ligtenberg MJ, Vos HL, Litvinov SV (1992) Cell membrane-associated mucins and their adhesion-modulating property. Trends Biochem Sci 17:359–363PubMedCrossRefGoogle Scholar
  16. 16.
    Kim YS (1992) Altered glycosylation of mucin glycoproteins in colonic neoplasia. J Cell Biochem Suppl 16G:91–96PubMedCrossRefGoogle Scholar
  17. 17.
    Verfaillie CM (1998) Adhesion receptors as regulators of the hematopoietic process. Blood 92:2609–2612PubMedGoogle Scholar
  18. 18.
    Taylor-Papadimitriou J (1991) Report on the first international workshop on carcinoma-associated mucins. Int J Cancer 49:1–5PubMedCrossRefGoogle Scholar
  19. 19.
    Mason D, Andre P, Bensussan A, Buckley C, Civin C, Clark E, de Haas M, Goyert S, Hadam M, Hart D, Horejsi V, Meuer S, Morrissey J, Schwartz-Albiez R, Shaw S, Simmons D, Uguccioni M, van der Schoot E, Vivier E, Zola H (2002) Reference: CD Antigens 2002. J Immunol 168:2083–2086PubMedCrossRefGoogle Scholar
  20. 20.
    Brayman M, Thathiah A, Carson DD (2004) MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod Biol Endocrinol RB&E 2:4CrossRefGoogle Scholar
  21. 21.
    Wreschner DH, McGuckin MA, Williams SJ, Baruch A, Yoeli M, Ziv R, Okun L, Zaretsky J, Smorodinsky N, Keydar I, Neophytou P, Stacey M, Lin HH, Gordon S (2002) Generation of ligand-receptor alliances by “SEA” module-mediated cleavage of membrane-associated mucin proteins. Protein Sci 11:698–706PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Spicer AP, Parry G, Patton S, Gendler SJ (1991) Molecular cloning and analysis of the mouse homologue of the tumor-associated mucin, MUC1, reveals conservation of potential O-glycosylation sites, transmembrane, and cytoplasmic domains and a loss of minisatellite-like polymorphism. J Biol Chem 266:15099–15109PubMedGoogle Scholar
  23. 23.
    Vos HL, de Vries Y, Hilkens J (1991) The mouse episialin (Muc1) gene and its promoter: rapid evolution of the repetitive domain in the protein. Biochem Biophys Res Commun 181:121–130PubMedCrossRefGoogle Scholar
  24. 24.
    Hanisch FG, Muller S, Hassan H, Clausen H, Zachara N, Gooley AA, Paulsen H, Alving K, Peter-Katalinic J (1999) Dynamic epigenetic regulation of initial O-glycosylation by UDP-N-Acetylgalactosamine: peptide N-acetylgalactosaminyltransferases. site-specific glycosylation of MUC1 repeat peptide influences the substrate qualities at adjacent or distant Ser/Thr positions. J Biol Chem 274:9946–9954PubMedCrossRefGoogle Scholar
  25. 25.
    Muller S, Alving K, Peter-Katalinic J, Zachara N, Gooley AA, Hanisch FG (1999) High density O-glycosylation on tandem repeat peptide from secretory MUC1 of T47D breast cancer cells. J Biol Chem 274:18165–18172PubMedCrossRefGoogle Scholar
  26. 26.
    Xing PX, Prenzoska J, McKenzie IF (1992) Epitope mapping of anti-breast and anti-ovarian mucin monoclonal antibodies. Mol Immunol 29:641–650PubMedCrossRefGoogle Scholar
  27. 27.
    Fontenot JD, Tjandra N, Bu D, Ho C, Montelaro RC, Finn OJ (1993) Biophysical characterization of one-, two-, and three-tandem repeats of human mucin (muc-1) protein core. Cancer Res 53:5386–5394PubMedGoogle Scholar
  28. 28.
    Schuman J, Campbell AP, Koganty RR, Longenecker BM (2003) Probing the conformational and dynamical effects of O-glycosylation within the immunodominant region of a MUC1 peptide tumor antigen. J Pept Res 61:91–108PubMedCrossRefGoogle Scholar
  29. 29.
    Price MR (1988) High molecular weight epithelial mucins as markers in breast cancer. Euro J Cancer Clin Oncol 24:1799–1804CrossRefGoogle Scholar
  30. 30.
    Price MR, Hudecz F, O’Sullivan C, Baldwin RW, Edwards PM, Tendler SJ (1990) Immunological and structural features of the protein core of human polymorphic epithelial mucin. Mol Immunol 27:795–802PubMedCrossRefGoogle Scholar
  31. 31.
    Burchell J, Taylor-Papadimitriou J, Boshell M, Gendler S, Duhig T (1989) A short sequence, within the amino acid tandem repeat of a cancer-associated mucin, contains immunodominant epitopes. Int J Cancer 44:691–696PubMedCrossRefGoogle Scholar
  32. 32.
    Tendler SJ (1990) Elements of secondary structure in a human epithelial mucin core peptide fragment. Biochem J 267:733–737PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Dziadek S, Griesinger C, Kunz H, Reinscheid UM (2006) Synthesis and structural model of an alpha(2,6)-sialyl-t glycosylated MUC1 eicosapeptide under physiological conditions. Chemistry 12:4981–4993PubMedCrossRefGoogle Scholar
  34. 34.
    Muller S, Hanisch FG (2002) Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. High density and prevalent core 2-based glycosylation. J Biol Chem 277:26103–26112PubMedCrossRefGoogle Scholar
  35. 35.
    Apostolopoulos V, Haurum JS, McKenzie IF (1997) MUC1 peptide epitopes associated with five different H-2 class I molecules. Eur J Immunol 27:2579–2587PubMedCrossRefGoogle Scholar
  36. 36.
    Apostolopoulos V, Karanikas V, Haurum JS, McKenzie IF (1997) Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen. J Immunol 159:5211–5218PubMedGoogle Scholar
  37. 37.
    Apostolopoulos V, Loveland BE, Pietersz GA, McKenzie IF (1995) CTL in mice immunized with human mucin 1 are MHC-restricted. J Immunol 155:5089–5094PubMedGoogle Scholar
  38. 38.
    Apostolopoulos V, Pietersz GA, Loveland BE, Sandrin MS, McKenzie IF (1995) Oxidative/reductive conjugation of mannan to antigen selects for T1 or T2 immune responses. Proc Natl Acad Sci 92:10128–10132PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Apostolopoulos V, Pietersz GA, Xing PX, Lees CJ, Michael M, Bishop J, McKenzie IF (1995) The immunogenicity of MUC1 peptides and fusion protein. Cancer Lett 90:21–26PubMedCrossRefGoogle Scholar
  40. 40.
    Apostolopoulos V, Xing PX, Trapani JA, McKenzie IF (1993) Production of anti-breast cancer monoclonal antibodies using a glutathione-S-transferase-MUC1 bacterial fusion protein. Br J Cancer 67:713–720PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Lofthouse SA, Apostolopoulos V, Pietersz GA, Li W, McKenzie IF (1997) Induction of T1 (cytotoxic lymphocyte) and/or T2 (antibody) responses to a mucin-1 tumour antigen. Vaccine 15:1586–1593PubMedCrossRefGoogle Scholar
  42. 42.
    Nishimori I, Perini F, Mountjoy KP, Sanderson SD, Johnson N, Cerny RL, Gross ML, Fontenot JD, Hollingsworth MA (1994) N-acetylgalactosamine glycosylation of MUC1 tandem repeat peptides by pancreatic tumor cell extracts. Cancer Res 54:3738–3744PubMedGoogle Scholar
  43. 43.
    Kirnarsky L, Prakash O, Vogen SM, Nomoto M, Hollingsworth MA, Sherman S (2000) Structural effects of O-glycosylation on a 15-residue peptide from the mucin (MUC1) core protein. Biochemistry 39:12076–12082PubMedCrossRefGoogle Scholar
  44. 44.
    Fackenthal JD, Godley LA (2008) Aberrant RNA splicing and its functional consequences in cancer cells. Dis Model Mech 1:37–42PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Obermair A, Schmid BC, Stimpfl M, Fasching B, Preyer O, Leodolter S, Crandon AJ, Zeillinger R (2001) Novel MUC1 splice variants are expressed in cervical carcinoma. Gynecol Oncol 83:343–347PubMedCrossRefGoogle Scholar
  46. 46.
    Zhang L, Vlad A, Milcarek C, Finn OJ (2013) Human mucin MUC1 RNA undergoes different types of alternative splicing resulting in multiple isoforms. Cancer Immunol Immunother: CII 62:423–435PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Smorodinsky N, Weiss M, Hartmann ML, Baruch A, Harness E, Yaakobovitz M, Keydar I, Wreschner DH (1996) Detection of a secreted MUC1/SEC protein by MUC1 isoform specific monoclonal antibodies. Biochem Biophys Res Commun 228:115–121PubMedCrossRefGoogle Scholar
  48. 48.
    Xing PX, Apostolopoulos V, Karkaloutsos J, McKenzie IF (2000) Monoclonal antibodies to mucin VNTR peptides. Methods Mol Biol 125:369–381PubMedGoogle Scholar
  49. 49.
    Xing PX, Apostolopoulos V, Pietersz G, McKenzie IF (2001) Anti-mucin monoclonal antibodies. Front Biosci 6:D1284–D1295PubMedCrossRefGoogle Scholar
  50. 50.
    Obermair A, Schmid BC, Packer LM, Leodolter S, Birner P, Ward BG, Crandon AJ, McGuckin MA, Zeillinger R (2002) Expression of MUC1 splice variants in benign and malignant ovarian tumours. Int J Cancer 100:166–171PubMedCrossRefGoogle Scholar
  51. 51.
    Hey NA, Meseguer M, Simon C, Smorodinsky NI, Wreschner DH, Ortiz ME, Aplin JD (2003) Transmembrane and truncated (SEC) isoforms of MUC1 in the human endometrium and Fallopian tube. Reprod Biol Endocrinol 1:2PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Hartman M, Baruch A, Ron I, Aderet Y, Yoeli M, Sagi-Assif O, Greenstein S, Stadler Y, Weiss M, Harness E, Yaakubovits M, Keydar I, Smorodinsky NI, Wreschner DH (1999) MUC1 isoform specific monoclonal antibody 6E6/2 detects preferential expression of the novel MUC1/Y protein in breast and ovarian cancer. Int J Cancer 82:256–267PubMedCrossRefGoogle Scholar
  53. 53.
    Wesseling J, van der Valk SW, Vos HL, Sonnenberg A, Hilkens J (1995) Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J Cell Biol 129:255–265PubMedCrossRefGoogle Scholar
  54. 54.
    Schmid BC, Rudas M, Fabjani G, Speiser P, Kaserer K, Leodolter S, Zeillinger R (2003) Evaluation of MUC1 splice variants as prognostic markers in patients with ductal carcinoma in situ of the breast. Oncol Rep 10:1981–1985PubMedGoogle Scholar
  55. 55.
    Meerzaman D, Xing PX, Kim KC (2000) Construction and characterization of a chimeric receptor containing the cytoplasmic domain of MUC1 mucin, American journal of physiology. Lung Cell Mol Physiol 278:L625–L629Google Scholar
  56. 56.
    Zrihan-Licht S, Baruch A, Elroy-Stein O, Keydar I, Wreschner DH (1994) Tyrosine phosphorylation of the MUC1 breast cancer membrane proteins. Cytokine receptor-like molecules. FEBS Lett 356:130–136PubMedCrossRefGoogle Scholar
  57. 57.
    Baruch A, Hartmann M, Yoeli M, Adereth Y, Greenstein S, Stadler Y, Skornik Y, Zaretsky J, Smorodinsky NI, Keydar I, Wreschner DH (1999) The breast cancer-associated MUC1 gene generates both a receptor and its cognate binding protein. Cancer Res 59:1552–1561PubMedGoogle Scholar
  58. 58.
    Baruch A, Hartmann M, Zrihan-Licht S, Greenstein S, Burstein M, Keydar I, Weiss M, Smorodinsky N, Wreschner DH (1997) Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function. Int J Cancer 71:741–749PubMedCrossRefGoogle Scholar
  59. 59.
    Levitin F, Baruch A, Weiss M, Stiegman K, Hartmann ML, Yoeli-Lerner M, Ziv R, Zrihan-Licht S, Shina S, Gat A, Lifschitz B, Simha M, Stadler Y, Cholostoy A, Gil B, Greaves D, Keydar I, Zaretsky J, Smorodinsky N, Wreschner DH (2005) A novel protein derived from the MUC1 gene by alternative splicing and frameshifting. J Biol Chem 280:10655–10663PubMedCrossRefGoogle Scholar
  60. 60.
    Levitin F, Stern O, Weiss M, Gil-Henn C, Ziv R, Prokocimer Z, Smorodinsky NI, Rubinstein DB, Wreschner DH (2005) The MUC1 SEA module is a self-cleaving domain. J Biol Chem 280:33374–33386PubMedCrossRefGoogle Scholar
  61. 61.
    Imbert Y, Darling DS, Jumblatt MM, Foulks GN, Couzin EG, Steele PS, Young WW Jr (2006) MUC1 splice variants in human ocular surface tissues: possible differences between dry eye patients and normal controls. Exp Eye Res 83:493–501PubMedCrossRefGoogle Scholar
  62. 62.
    Imbert Y, Foulks GN, Brennan MD, Jumblatt MM, John G, Shah HA, Newton C, Pouranfar F, Young WW Jr (2009) MUC1 and estrogen receptor alpha gene polymorphisms in dry eye patients. Exp Eye Res 88:334–338PubMedCrossRefGoogle Scholar
  63. 63.
    Imbert-Fernandez Y, Radde BN, Teng Y, Young WW Jr, Hu C, Klinge CM (2011) MUC1/A and MUC1/B splice variants differentially regulate inflammatory cytokine expression. Exp Eye Res 93:649–657PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Strawbridge RJ, Nister M, Brismar K, Li C, Lindstrom S (2008) Influence of MUC1 genetic variation on prostate cancer risk and survival. Eur J Hum Gen 16:1521–1525CrossRefGoogle Scholar
  65. 65.
    Hikita ST, Kosik KS, Clegg DO, Bamdad C (2008) MUC1* mediates the growth of human pluripotent stem cells. PLoS One 3:e3312PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Ligtenberg MJ, Kruijshaar L, Buijs F, van Meijer M, Litvinov SV, Hilkens J (1992) Cell-associated episialin is a complex containing two proteins derived from a common precursor. J Biol Chem 267:6171–6177PubMedGoogle Scholar
  67. 67.
    Raina D, Ahmad R, Rajabi H, Panchamoorthy G, Kharbanda S, Kufe D (2012) Targeting cysteine-mediated dimerization of the MUC1-C oncoprotein in human cancer cells. Int J Oncol 40:1643–1649PubMedCentralPubMedGoogle Scholar
  68. 68.
    Kufe DW (2013) MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches. Oncogene 32:1073–1081PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Kumar P, Lindberg L, Thirkill TL, Ji JW, Martsching L, Douglas GC (2012) The MUC1 extracellular domain subunit is found in nuclear speckles and associates with spliceosomes. PLoS One 7:e42712PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Pitroda SP, Khodarev NN, Beckett MA, Kufe DW, Weichselbaum RR (2009) MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment. Proc Natl Acad Sci 106:5837–5841PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Kosugi M, Ahmad R, Alam M, Uchida Y, Kufe D (2011) MUC1-C oncoprotein regulates glycolysis and pyruvate kinase M2 activity in cancer cells. PLoS One 6:e28234PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Joshi MD, Ahmad R, Yin L, Raina D, Rajabi H, Bubley G, Kharbanda S, Kufe D (2009) MUC1 oncoprotein is a druggable target in human prostate cancer cells. Mol Cancer Ther 8:3056–3065PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Raina D, Ahmad R, Joshi MD, Yin L, Wu Z, Kawano T, Vasir B, Avigan D, Kharbanda S, Kufe D (2009) Direct targeting of the mucin 1 oncoprotein blocks survival and tumorigenicity of human breast carcinoma cells. Cancer Res 69:5133–5141PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Raina D, Kosugi M, Ahmad R, Panchamoorthy G, Rajabi H, Alam M, Shimamura T, Shapiro GI, Supko J, Kharbanda S, Kufe D (2011) Dependence on the MUC1-C oncoprotein in non-small cell lung cancer cells. Mol Cancer Ther 10:806–816PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Yin L, Ahmad R, Kosugi M, Kawano T, Avigan D, Stone R, Kharbanda S, Kufe D (2010) Terminal differentiation of chronic myelogenous leukemia cells is induced by targeting of the MUC1-C oncoprotein. Cancer Biol Ther 10:483–491PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Yin L, Ahmad R, Kosugi M, Kufe T, Vasir B, Avigan D, Kharbanda S, Kufe D (2010) Survival of human multiple myeloma cells is dependent on MUC1 C-terminal transmembrane subunit oncoprotein function. Mol Pharmacol 78:166–174PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Yin L, Kosugi M, Kufe D (2012) Inhibition of the MUC1-C oncoprotein induces multiple myeloma cell death by down-regulating TIGAR expression and depleting NADPH. Blood 119:810–816PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Yin L, Kufe D (2011) MUC1-C oncoprotein blocks terminal differentiation of chronic myelogenous leukemia cells by a ROS-mediated mechanism. Genes Cancer 2:56–64PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Klinge CM, Radde BN, Imbert-Fernandez Y, Teng Y, Ivanova MM, Abner SM, Martin AL (2011) Targeting the intracellular MUC1 C-terminal domain inhibits proliferation and estrogen receptor transcriptional activity in lung adenocarcinoma cells. Mol Cancer Ther 10:2062–2071PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Gendler SJ (2001) MUC1, the renaissance molecule. J Mammary Gland Biol Neoplasia 6:339–353PubMedCrossRefGoogle Scholar
  81. 81.
    Kufe D, Inghirami G, Abe M, Hayes D, Justi-Wheeler H, Schlom J (1984) Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma 3:223–232PubMedCrossRefGoogle Scholar
  82. 82.
    Seregni E, Botti C, Massaron S, Lombardo C, Capobianco A, Bogni A, Bombardieri E (1997) Structure, function and gene expression of epithelial mucins. Tumori 83:625–632PubMedGoogle Scholar
  83. 83.
    Kuroda H, Mun M, Okumura S, Nakagawa K (2012) Segmentectomy for giant pulmonary sclerosing haemangiomas with high serum KL-6 levels. Interact CardioVasc Thorac Surg 15:171–173PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Terada T (2008) Ductal adenoma of the breast: immunohistochemistry of two cases. Pathol Int 58:801–805PubMedCrossRefGoogle Scholar
  85. 85.
    Xing PX, Tjandra JJ, Reynolds K, McLaughlin PJ, Purcell DF, McKenzie IF (1989) Reactivity of anti-human milk fat globule antibodies with synthetic peptides. J Immunol 142:3503–3509PubMedGoogle Scholar
  86. 86.
    Xing PX, Tjandra JJ, Stacker SA, Teh JG, Thompson CH, McLaughlin PJ, McKenzie IF (1989) Monoclonal antibodies reactive with mucin expressed in breast cancer. Immunol Cell Biol 67(Pt 3):183–195PubMedCrossRefGoogle Scholar
  87. 87.
    Blalock TD, Spurr-Michaud SJ, Tisdale AS, Gipson IK (2008) Release of membrane-associated mucins from ocular surface epithelia. Invest Ophthalmol Vis Sci 49:1864–1871PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Ando I, Kukita A, Soma G, Hino H (1998) A large number of tandem repeats in the polymorphic epithelial mucin gene is associated with severe acne. J Dermatol 25:150–152PubMedCrossRefGoogle Scholar
  89. 89.
    Jung SE, Seo KY, Kim H, Kim HL, Chung IH, Kim EK (2002) Expression of MUC1 on corneal endothelium of human. Cornea 21:691–695PubMedCrossRefGoogle Scholar
  90. 90.
    Corrales RM, Narayanan S, Fernandez I, Mayo A, Galarreta DJ, Fuentes-Paez G, Chaves FJ, Herreras JM, Calonge M (2011) Ocular mucin gene expression levels as biomarkers for the diagnosis of dry eye syndrome. Invest Ophthalmol Vis Sci 52:8363–8369PubMedCrossRefGoogle Scholar
  91. 91.
    Kerschner JE (2007) Mucin gene expression in human middle ear epithelium. Laryngoscope 117:1666–1676PubMedCrossRefGoogle Scholar
  92. 92.
    Kamoshida S, Tsutsumi Y (1998) Expression of MUC-1 glycoprotein in plasma cells, follicular dendritic cells, myofibroblasts and perineurial cells: immunohistochemical analysis using three monoclonal antibodies. Pathol Int 48:776–785PubMedCrossRefGoogle Scholar
  93. 93.
    Engelmann K, Shen H, Finn OJ (2008) MCF7 side population cells with characteristics of cancer stem/progenitor cells express the tumor antigen MUC1. Cancer Res 68:2419–2426PubMedCrossRefGoogle Scholar
  94. 94.
    Wang HH, Afdhal NH, Gendler SJ, Wang DQ (2004) Targeted disruption of the murine mucin gene 1 decreases susceptibility to cholesterol gallstone formation. J Lipid Res 45:438–447PubMedCrossRefGoogle Scholar
  95. 95.
    Wang HH, Afdhal NH, Gendler SJ, Wang DQ (2006) Evidence that gallbladder epithelial mucin enhances cholesterol cholelithogenesis in MUC1 transgenic mice. Gastroenterology 131:210–222PubMedCrossRefGoogle Scholar
  96. 96.
    Sasaki M, Nakanuma Y (1996) Frequent expression of MUC1 apomucin on biliary epithelial cells of damaged small bile ducts in primary biliary cirrhosis and chronic viral hepatitis: an immunohistochemical study. Hepatology 23:1313–1317PubMedCrossRefGoogle Scholar
  97. 97.
    Carson DD, DeSouza MM, Kardon R, Zhou X, Lagow E, Julian J (1998) Mucin expression and function in the female reproductive tract. Human Reprod Update 4:459–464CrossRefGoogle Scholar
  98. 98.
    DeLoia JA, Krasnow JS, Brekosky J, Babaknia A, Julian J, Carson DD (1998) Regional specialization of the cell membrane-associated, polymorphic mucin (MUC1) in human uterine epithelia. Hum Reprod 13:2902–2909PubMedCrossRefGoogle Scholar
  99. 99.
    DeSouza MM, Surveyor GA, Price RE, Julian J, Kardon R, Zhou X, Gendler S, Hilkens J, Carson DD (1999) MUC1/episialin: a critical barrier in the female reproductive tract. J Reprod Immunol 45:127–158PubMedCrossRefGoogle Scholar
  100. 100.
    Jeschke U, Richter DU, Hammer A, Briese V, Friese K, Karsten U (2002) Expression of the Thomsen-Friedenreich antigen and of its putative carrier protein mucin 1 in the human placenta and in trophoblast cells in vitro. Histochem Cell Biol 117:219–226PubMedCrossRefGoogle Scholar
  101. 101.
    Meseguer M, Aplin JD, Caballero-Campo P, O’Connor JE, Martin JC, Remohi J, Pellicer A, Simon C (2001) Human endometrial mucin MUC1 is up-regulated by progesterone and down-regulated in vitro by the human blastocyst. Biol Reprod 64:590–601PubMedCrossRefGoogle Scholar
  102. 102.
    Aplin JD, Meseguer M, Simon C, Ortiz ME, Croxatto H, Jones CJ (2001) MUC1, glycans and the cell-surface barrier to embryo implantation. Biochem Soc Trans 29:153–156PubMedCrossRefGoogle Scholar
  103. 103.
    Dharmaraj N, Gendler SJ, Carson DD (2009) Expression of human MUC1 during early pregnancy in the human MUC1 transgenic mouse model. Biol Reprod 81:1182–1188PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Ren S, Wang X, Ma B, Yuan Q, Zhang H, Yu X, Hao A (2011) Arnebia preventing the expression of Muc1 protein decrease results in anti-implantation in early pregnant mice. Contraception 83:378–384PubMedCrossRefGoogle Scholar
  105. 105.
    Albaghdadi AJ, Kan FW (2012) Endometrial receptivity defects and impaired implantation in diabetic NOD mice. Biol Reprod 87:30PubMedCentralPubMedCrossRefGoogle Scholar
  106. 106.
    Shyu MK, Chen CW, Lin NY, Liao WC, Chen CH, Lin CJ, Huang HC, Lee JJ, Huang MJ, Tseng GF, Shih JC, Lee CN, Hsieh FJ, Huang MC (2011) MUC1 expression is elevated in severe preeclamptic placentas and suppresses trophoblast cell invasion via beta1-integrin signaling. J Clin Endocrinol Metab 96:3759–3767PubMedCrossRefGoogle Scholar
  107. 107.
    Xu B, Sun X, Li L, Wu L, Zhang A, Feng Y (2012) Pinopodes, leukemia inhibitory factor, integrin-beta3, and mucin-1 expression in the peri-implantation endometrium of women with unexplained recurrent pregnancy loss. Fertil Steril 98:389–395PubMedCrossRefGoogle Scholar
  108. 108.
    Bozdag G, Atak ZG, Yapici Z, Demirol A, Usubutun A, Gurgan T (2011) Five recurrent ectopic pregnancies in a patient with MUC1 expression deficiency. J Obstet Gynaecol 31:666–667PubMedCrossRefGoogle Scholar
  109. 109.
    Margarit L, Taylor A, Roberts MH, Hopkins L, Davies C, Brenton AG, Conlan RS, Bunkheila A, Joels L, White JO, Gonzalez D (2010) MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. J Clin Endocrinol Metab 95:5320–5329PubMedCrossRefGoogle Scholar
  110. 110.
    Reza HM, Ng BY, Phan TT, Tan DT, Beuerman RW, Ang LP (2011) Characterization of a novel umbilical cord lining cell with CD227 positivity and unique pattern of P63 expression and function. Stem Cell Rev 7:624–638PubMedCrossRefGoogle Scholar
  111. 111.
    Franke FE, Kraus S, Eiermann C, Pauls K, Lalani EN, Bergmann M (2001) MUC1 in normal and impaired spermatogenesis. Mol Hum Reprod 7:505–512PubMedCrossRefGoogle Scholar
  112. 112.
    Huminiecki L, Chan HY, Lui S, Poulsom R, Stamp G, Harris AL, Bicknell R (2001) Vascular endothelial growth factor transgenic mice exhibit reduced male fertility and placental rejection. Mol Hum Reprod 7:255–264PubMedCrossRefGoogle Scholar
  113. 113.
    Agrawal B, Krantz MJ, Parker J, Longenecker BM (1998) Expression of MUC1 mucin on activated human T cells: implications for a role of MUC1 in normal immune regulation. Cancer Res 58:4079–4081PubMedGoogle Scholar
  114. 114.
    Chadburn A, Inghirami G, Knowles DM (1992) T-cell activation-associated antigen expression by neoplastic T-cells. Hematol Pathol 6:131–141PubMedGoogle Scholar
  115. 115.
    Chadburn A, Inghirami G, Knowles DM (1992) The kinetics and temporal expression of T-cell activation-associated antigens CD15 (LeuM1), CD30 (Ki-1), EMA, and CD11c (LeuM5) by benign activated T cells. Hematol Pathol 6:193–202PubMedGoogle Scholar
  116. 116.
    Fattorossi A, Battaglia A, Malinconico P, Stoler A, Andreocci L, Parente D, Coscarella A, Maggiano N, Perillo A, Pierelli L, Scambia G (2002) Constitutive and inducible expression of the epithelial antigen MUC1 (CD227) in human T cells. Exp Cell Res 280:107–118PubMedCrossRefGoogle Scholar
  117. 117.
    Wykes M, MacDonald KP, Tran M, Quin RJ, Xing PX, Gendler SJ, Hart DN, McGuckin MA (2002) MUC1 epithelial mucin (CD227) is expressed by activated dendritic cells. J Leukoc Biol 72:692–701PubMedGoogle Scholar
  118. 118.
    Treon SP, Mollick JA, Urashima M, Teoh G, Chauhan D, Ogata A, Raje N, Hilgers JH, Nadler L, Belch AR, Pilarski LM, Anderson KC (1999) Muc-1 core protein is expressed on multiple myeloma cells and is induced by dexamethasone. Blood 93:1287–1298PubMedGoogle Scholar
  119. 119.
    Correa I, Plunkett T, Vlad A, Mungul A, Candelora-Kettel J, Burchell JM, Taylor-Papadimitriou J, Finn OJ (2003) Form and pattern of MUC1 expression on T cells activated in vivo or in vitro suggests a function in T-cell migration. Immunology 108:32–41PubMedCentralPubMedCrossRefGoogle Scholar
  120. 120.
    Plunkett TA, Correa I, Miles DW, Taylor-Papadimitriou J (2001) Breast cancer and the immune system: opportunities and pitfalls. J Mammary Gland Biol Neoplasia 6:467–475PubMedCrossRefGoogle Scholar
  121. 121.
    Agrawal B, Longenecker BM (2005) MUC1 mucin-mediated regulation of human T cells. Int Immunol 17:391–399PubMedCrossRefGoogle Scholar
  122. 122.
    Konowalchuk JD, Agrawal B (2012) MUC1 is a novel costimulatory molecule of human T cells and functions in an AP-1-dependent manner. Hum Immunol 73:448–455PubMedCrossRefGoogle Scholar
  123. 123.
    Vasir B, Avigan D, Wu Z, Crawford K, Turnquist S, Ren J, Kufe D (2005) Dendritic cells induce MUC1 expression and polarization on human T cells by an IL-7-dependent mechanism. J Immun 174:2376–2386PubMedCrossRefGoogle Scholar
  124. 124.
    Mukherjee P, Tinder TL, Basu GD, Gendler SJ (2005) MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells. J Leukoc Biol 77:90–99PubMedGoogle Scholar
  125. 125.
    Cloosen S, Thio M, Vanclee A, van Leeuwen EB, Senden-Gijsbers BL, Oving EB, Germeraad WT, Bos GM (2004) Mucin-1 is expressed on dendritic cells, both in vitro and in vivo. Int Immunol 16:1561–1571PubMedCrossRefGoogle Scholar
  126. 126.
    Rughetti A, Pellicciotta I, Biffoni M, Backstrom M, Link T, Bennet EP, Clausen H, Noll T, Hansson GC, Burchell JM, Frati L, Taylor-Papadimitriou J, Nuti M (2005) Recombinant tumor-associated MUC1 glycoprotein impairs the differentiation and function of dendritic cells. J Immunol 174:7764–7772PubMedCrossRefGoogle Scholar
  127. 127.
    Carlos CA, Dong HF, Howard OM, Oppenheim JJ, Hanisch FG, Finn OJ (2005) Human tumor antigen MUC1 is chemotactic for immature dendritic cells and elicits maturation but does not promote Th1 type immunity. J Immunol 175:1628–1635PubMedCrossRefGoogle Scholar
  128. 128.
    Williams MA, Bauer S, Lu W, Guo J, Walter S, Bushnell TP, Lillehoj EP, Georas SN (2010) Deletion of the mucin-like molecule muc1 enhances dendritic cell activation in response to toll-like receptor ligands. J Innate Immun 2:123–143PubMedCentralPubMedCrossRefGoogle Scholar
  129. 129.
    Ilkovitch D, Lopez DM (2009) Urokinase-mediated recruitment of myeloid-derived suppressor cells and their suppressive mechanisms are blocked by MUC1/sec. Blood 113:4729–4739PubMedCentralPubMedCrossRefGoogle Scholar
  130. 130.
    Poh TW, Bradley JM, Mukherjee P, Gendler SJ (2009) Lack of Muc1-regulated beta-catenin stability results in aberrant expansion of CD11b + Gr1 + myeloid-derived suppressor cells from the bone marrow. Cancer Res 69:3554–3562PubMedCentralPubMedCrossRefGoogle Scholar
  131. 131.
    Brugger W, Buhring HJ, Grunebach F, Vogel W, Kaul S, Muller R, Brummendorf TH, Ziegler BL, Rappold I, Brossart P, Scheding S, Kanz L (1999) Expression of MUC-1 epitopes on normal bone marrow: implications for the detection of micrometastatic tumor cells. J Clin Oncol 17:1535–1544PubMedGoogle Scholar
  132. 132.
    Rughetti A, Biffoni M, Pierelli L, Rahimi H, Bonanno G, Barachini S, Pellicciotta I, Napoletano C, Pescarmona E, Del Nero A, Pignoloni P, Frati L, Nuti M (2003) Regulated expression of MUC1 epithelial antigen in erythropoiesis. Br J Haematol 120:344–352PubMedCrossRefGoogle Scholar
  133. 133.
    Norris AM, Gore A, Balboni A, Young A, Longnecker DS, Korc M (2013) AGR2 is a SMAD4-suppressible gene that modulates MUC1 levels and promotes the initiation and progression of pancreatic intraepithelial neoplasia. Oncogene 32:3867–3876PubMedCentralPubMedCrossRefGoogle Scholar
  134. 134.
    Paszkiewicz-Gadek A, Porowska H, Pietruczuk M, Haczynski J, Kisiel DG, Wolczynski S (2005) Effect of estradiol and raloxifene on MUC1 expression and adhesive properties of Ishikawa cells. Oncol Rep 14:583–589PubMedGoogle Scholar
  135. 135.
    Dharmaraj N, Wang P, Carson DD (2010) Cytokine and progesterone receptor interplay in the regulation of MUC1 gene expression. Mol Endocrinol 24:2253–2266PubMedCentralPubMedCrossRefGoogle Scholar
  136. 136.
    Koga T, Kuwahara I, Lillehoj EP, Lu W, Miyata T, Isohama Y, Kim KC (2007) TNF-alpha induces MUC1 gene transcription in lung epithelial cells: its signaling pathway and biological implication. Am J Physiol Lung Cell Mole Physiol 293:L693–L701CrossRefGoogle Scholar
  137. 137.
    Kim SW, Seo KY, Rhim T, Kim EK (2012) Effect of retinoic acid on epithelial differentiation and mucin expression in primary human corneal limbal epithelial cells. Curr Eye Res 37:33–42PubMedCrossRefGoogle Scholar
  138. 138.
    Seo KY, Chung SH, Lee JH, Park MY, Kim EK (2007) Regulation of membrane-associated mucins in the human corneal epithelial cells by dexamethasone. Cornea 26:709–714PubMedCrossRefGoogle Scholar
  139. 139.
    Takeji Y, Urashima H, Aoki A, Shinohara H (2012) Rebamipide increases the mucin-like glycoprotein production in corneal epithelial cells. J Ocular Pharmacol Ther 28:259–263CrossRefGoogle Scholar
  140. 140.
    Kuwahara I, Lillehoj EP, Koga T, Isohama Y, Miyata T, Kim KC (2007) The signaling pathway involved in neutrophil elastase stimulated MUC1 transcription. Am J Respir Cell Mol Biol 37:691–698PubMedCentralPubMedCrossRefGoogle Scholar
  141. 141.
    Rajabi H, Joshi MD, Jin C, Ahmad R, Kufe D (2011) Androgen receptor regulates expression of the MUC1-C oncoprotein in human prostate cancer cells. Prostate 71:1299–1308PubMedGoogle Scholar
  142. 142.
    Verma M, Davidson EA (1999) MUC1 upregulation by ethanol. Cancer Biochem Biophys 17:1–11PubMedGoogle Scholar
  143. 143.
    Jain JK, Li A, Minoo P, Nucatola DL, Felix JC (2005) The effect of nonoxynol-9 on human endometrium. Contraception 71:137–142PubMedCrossRefGoogle Scholar
  144. 144.
    Schroten H, Hanisch FG, Plogmann R, Hacker J, Uhlenbruck G, Nobis-Bosch R, Wahn V (1992) Inhibition of adhesion of S-fimbriated Escherichia coli to buccal epithelial cells by human milk fat globule membrane components: a novel aspect of the protective function of mucins in the nonimmunoglobulin fraction. Infect Immun 60:2893–2899PubMedCentralPubMedGoogle Scholar
  145. 145.
    Yolken RH, Peterson JA, Vonderfecht SL, Fouts ET, Midthun K, Newburg DS (1992) Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis. J Clin Investig 90:1984–1991PubMedCentralPubMedCrossRefGoogle Scholar
  146. 146.
    Hilkens J, Wesseling J, Vos HL, Storm J, Boer B, van der Valk SW, Maas MC (1995) Involvement of the cell surface-bound mucin, episialin/MUC1, in progression of human carcinomas. Biochem Soc Trans 23:822–826PubMedCrossRefGoogle Scholar
  147. 147.
    Ligtenberg MJ, Buijs F, Vos HL, Hilkens J (1992) Suppression of cellular aggregation by high levels of episialin. Cancer Res 52:2318–2324PubMedGoogle Scholar
  148. 148.
    Parker P, Sando L, Pearson R, Kongsuwan K, Tellam RL, Smith S (2010) Bovine Muc1 inhibits binding of enteric bacteria to Caco-2 cells. Glycoconj J 27:89–97PubMedCrossRefGoogle Scholar
  149. 149.
    Hudson MJ, Stamp GW, Hollingsworth MA, Pignatelli M, Lalani EN (1996) MUC1 expressed in PanC1 cells decreases adhesion to type 1 collagen but increases contraction in collagen lattices. Am J Pathol 148:951–960PubMedCentralPubMedGoogle Scholar
  150. 150.
    Suwa T, Hinoda Y, Makiguchi Y, Takahashi T, Itoh F, Adachi M, Hareyama M, Imai K (1998) Increased invasiveness of MUC1 and cDNA-transfected human gastric cancer MKN74 cells. Int J Cancer 76:377–382PubMedCrossRefGoogle Scholar
  151. 151.
    Tsutsumida H, Swanson BJ, Singh PK, Caffrey TC, Kitajima S, Goto M, Yonezawa S, Hollingsworth MA (2006) RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells. Clin Cancer Res 12:2976–2987PubMedCrossRefGoogle Scholar
  152. 152.
    Cheng JP, Yan Y, Wang XY, Lu YL, Yuan YH, Jia J, Ren J (2011) MUC1-positive circulating tumor cells and MUC1 protein predict chemotherapeutic efficacy in the treatment of metastatic breast cancer. Chin J Cancer 30:54–61PubMedCentralPubMedCrossRefGoogle Scholar
  153. 153.
    Dorn DC, Harnack U, Pecher G (2004) Down-regulation of the human tumor antigen mucin by gemcitabine on the pancreatic cancer cell line capan-2. Anticancer Res 24:821–825PubMedGoogle Scholar
  154. 154.
    Mukherjee P, Basu GD, Tinder TL, Subramani DB, Bradley JM, Arefayene M, Skaar T, De Petris G (2009) Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition. J Immunol 182:216–224PubMedCentralPubMedCrossRefGoogle Scholar
  155. 155.
    Quoix E, Ramlau R, Westeel V, Papai Z, Madroszyk A, Riviere A, Koralewski P, Breton JL, Stoelben E, Braun D, Debieuvre D, Lena H, Buyse M, Chenard MP, Acres B, Lacoste G, Bastien B, Tavernaro A, Bizouarne N, Bonnefoy JY, Limacher JM (2011) Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial. Lancet Oncol 12:1125–1133PubMedCrossRefGoogle Scholar
  156. 156.
    Chaika NV, Gebregiworgis T, Lewallen ME, Purohit V, Radhakrishnan P, Liu X, Zhang B, Mehla K, Brown RB, Caffrey T, Yu F, Johnson KR, Powers R, Hollingsworth MA, Singh PK (2012) MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate metabolism in pancreatic cancer. Proc Natl Acad Sci 109:13787–13792PubMedCentralPubMedCrossRefGoogle Scholar
  157. 157.
    Hiltbold EM, Vlad AM, Ciborowski P, Watkins SC, Finn OJ (2000) The mechanism of unresponsiveness to circulating tumor antigen MUC1 is a block in intracellular sorting and processing by dendritic cells. J Immunol 165:3730–3741PubMedCrossRefGoogle Scholar
  158. 158.
    Saeland E, van Vliet SJ, Backstrom M, van den Berg VC, Geijtenbeek TB, Meijer GA, van Kooyk Y (2007) The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma. Cancer Immunol Immunother CII 56:1225–1236PubMedCrossRefGoogle Scholar
  159. 159.
    Nath D, Hartnell A, Happerfield L, Miles DW, Burchell J, Taylor-Papadimitriou J, Crocker PR (1999) Macrophage-tumour cell interactions: identification of MUC1 on breast cancer cells as a potential counter-receptor for the macrophage-restricted receptor, sialoadhesin. Immunology 98:213–219PubMedCentralPubMedCrossRefGoogle Scholar
  160. 160.
    Swanson BJ, McDermott KM, Singh PK, Eggers JP, Crocker PR, Hollingsworth MA (2007) MUC1 is a counter-receptor for myelin-associated glycoprotein (Siglec-4a) and their interaction contributes to adhesion in pancreatic cancer perineural invasion. Cancer Res 67:10222–10229PubMedCrossRefGoogle Scholar
  161. 161.
    Fanayan S, Shehata M, Agterof AP, McGuckin MA, Alonso MA, Byrne JA (2009) Mucin 1 (MUC1) is a novel partner for MAL2 in breast carcinoma cells. BMC Cell Biol 10:7PubMedCentralPubMedCrossRefGoogle Scholar
  162. 162.
    Ramasamy S, Duraisamy S, Barbashov S, Kawano T, Kharbanda S, Kufe D (2007) The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Mol Cell 27:992–1004PubMedCentralPubMedCrossRefGoogle Scholar
  163. 163.
    Zhao Q, Barclay M, Hilkens J, Guo X, Barrow H, Rhodes JM, Yu LG (2010) Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Mole Cancer 9:154CrossRefGoogle Scholar
  164. 164.
    Zhao Q, Guo X, Nash GB, Stone PC, Hilkens J, Rhodes JM, Yu LG (2009) Circulating galectin-3 promotes metastasis by modifying MUC1 localization on cancer cell surface. Cancer Res 69:6799–6806PubMedCentralPubMedCrossRefGoogle Scholar
  165. 165.
    Barrow H, Guo X, Wandall HH, Pedersen JW, Fu B, Zhao Q, Chen C, Rhodes JM, Yu LG (2011) Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium. Clin Cancer Res 17:7035–7046PubMedCrossRefGoogle Scholar
  166. 166.
    Merlin J, Stechly L, de Beauce S, Monte D, Leteurtre E, van Seuningen I, Huet G, Pigny P (2011) Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells. Oncogene 30:2514–2525PubMedCrossRefGoogle Scholar
  167. 167.
    Lillehoj EP, Hyun SW, Feng C, Zhang L, Liu A, Guang W, Nguyen C, Luzina IG, Atamas SP, Passaniti A, Twaddell WS, Puche AC, Wang LX, Cross AS, Goldblum SE (2012) NEU1 sialidase expressed in human airway epithelia regulates epidermal growth factor receptor (EGFR) and MUC1 protein signaling. J Biol Chem 287:8214–8231PubMedCentralPubMedCrossRefGoogle Scholar
  168. 168.
    Yamamoto M, Bharti A, Li Y, Kufe D (1997) Interaction of the DF3/MUC1 breast carcinoma-associated antigen and beta-catenin in cell adhesion. J Biol Chem 272:12492–12494PubMedCrossRefGoogle Scholar
  169. 169.
    Strout HV, Vicario PP, Saperstein R, Slater EE (1988) A protein phosphotyrosine phosphatase distinct from alkaline phosphatase with activity against the insulin receptor. Biochem Biophys Res Commun 151:633–640PubMedCrossRefGoogle Scholar
  170. 170.
    Gunasekara N, Sykes B, Hugh J (2012) Characterization of a novel weak interaction between MUC1 and Src-SH3 using nuclear magnetic resonance spectroscopy. Biochem Biophys Res Commun 421:832–836PubMedCrossRefGoogle Scholar
  171. 171.
    Petersson S, Shubbar E, Yhr M, Kovacs A, Enerback C (2011) Loss of ICAM-1 signaling induces psoriasin (S100A7) and MUC1 in mammary epithelial cells. Breast Cancer Res Treat 125:13–25PubMedCrossRefGoogle Scholar
  172. 172.
    Geng Y, Yeh K, Takatani T, King MR (2012) Three to Tango: MUC1 as a Ligand for Both E-Selectin and ICAM-1 in the Breast Cancer Metastatic Cascade. Front Oncol 2:76PubMedCentralPubMedCrossRefGoogle Scholar
  173. 173.
    Yin L, Li Y, Ren J, Kuwahara H, Kufe D (2003) Human MUC1 carcinoma antigen regulates intracellular oxidant levels and the apoptotic response to oxidative stress. J Biol Chem 278:35458–35464PubMedCrossRefGoogle Scholar
  174. 174.
    Jin C, Rajabi H, Pitroda S, Li A, Kharbanda A, Weichselbaum R, Kufe D (2012) Cooperative interaction between the MUC1-C oncoprotein and the Rab31 GTPase in estrogen receptor-positive breast cancer cells. PLoS One 7:e39432PubMedCentralPubMedCrossRefGoogle Scholar
  175. 175.
    Kohlgraf KG, Gawron AJ, Higashi M, Meza JL, Burdick MD, Kitajima S, Kelly DL, Caffrey TC, Hollingsworth MA (2003) Contribution of the MUC1 tandem repeat and cytoplasmic tail to invasive and metastatic properties of a pancreatic cancer cell line. Cancer Res 63:5011–5020PubMedGoogle Scholar
  176. 176.
    Wang H, Lillehoj EP, Kim KC (2003) Identification of four sites of stimulated tyrosine phosphorylation in the MUC1 cytoplasmic tail. Biochem Biophys Res Commun 310:341–346PubMedCrossRefGoogle Scholar
  177. 177.
    Wreschner DH, Zrihan-Licht S, Baruch A, Sagiv D, Hartman ML, Smorodinsky N, Keydar I (1994) Does a novel form of the breast cancer marker protein, MUC1, act as a receptor molecule that modulates signal transduction? Adv Exp Med Biol 353:17–26PubMedCrossRefGoogle Scholar
  178. 178.
    Singh PK, Hollingsworth MA (2006) Cell surface-associated mucins in signal transduction. Trends Cell Biol 16:467–476PubMedCrossRefGoogle Scholar
  179. 179.
    Kufe DW (2009) Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 9:874–885PubMedCentralPubMedCrossRefGoogle Scholar
  180. 180.
    Carson DD (2008) The cytoplasmic tail of MUC1: a very busy place. Sci Signal 1:pe35Google Scholar
  181. 181.
    Mukhopadhyay P, Chakraborty S, Pnnusamy MP, Lakshmanan I, Jain M, Batra SK (1815) Mucins in the pathogenisis of breast cancer: implications in diagnosis, prognosis and therapy. Biochimica Biophys Acta 2011:224–240Google Scholar
  182. 182.
    Nath S, Mukherjee P (2014) MUC1: a multifaceted oncoprotein with a key role in cancer progression. Trends Mole Med 20:332–342CrossRefGoogle Scholar
  183. 183.
    Lillehoj EP, Kim BT, Kim KC (2002) Identification of Pseudomonas aeruginosa flagellin as an adhesin for Muc1 mucin. Am J Physiol Lung Cell Mole Physiol 282:L751–L756CrossRefGoogle Scholar
  184. 184.
    Lu W, Hisatsune A, Koga T, Kato K, Kuwahara I, Lillehoj EP, Chen W, Cross AS, Gendler SJ, Gewirtz AT, Kim KC (2006) Cutting edge: enhanced pulmonary clearance of Pseudomonas aeruginosa by Muc1 knockout mice. J Immunol 176:3890–3894PubMedCrossRefGoogle Scholar
  185. 185.
    Ueno K, Koga T, Kato K, Golenbock DT, Gendler SJ, Kai H, Kim KC (2008) MUC1 mucin is a negative regulator of toll-like receptor signaling. Am J Respir Cell Mol Biol 38:263–268PubMedCentralPubMedCrossRefGoogle Scholar
  186. 186.
    Li Y, Dinwiddie DL, Harrod KS, Jiang Y, Kim KC (2010) Anti-inflammatory effect of MUC1 during respiratory syncytial virus infection of lung epithelial cells in vitro. Am J Physiol Lung cellular and molecular physiology 298:L558–L563CrossRefGoogle Scholar
  187. 187.
    Kyo Y, Kato K, Park YS, Gajghate S, Umehara T, Lillehoj EP, Suzaki H, Kim KC (2012) Antiinflammatory role of MUC1 mucin during infection with nontypeable Haemophilus influenzae. Am J Respir Cell Mol Biol 46:149–156PubMedCentralPubMedCrossRefGoogle Scholar
  188. 188.
    Nguyen Y, Procario MC, Ashley SL, O’Neal WK, Pickles RJ, Weinberg JB (2011) Limited effects of Muc1 deficiency on mouse adenovirus type 1 respiratory infection. Virus Res 160:351–359PubMedCentralPubMedCrossRefGoogle Scholar
  189. 189.
    Byrd JC, Yunker CK, Xu QS, Sternberg LR, Bresalier RS (2000) Inhibition of gastric mucin synthesis by Helicobacter pylori. Gastroenterology 118:1072–1079PubMedCrossRefGoogle Scholar
  190. 190.
    Vinall LE, King M, Novelli M, Green CA, Daniels G, Hilkens J, Sarner M, Swallow DM (2002) Altered expression and allelic association of the hypervariable membrane mucin MUC1 in Helicobacter pylori gastritis. Gastroenterology 123:41–49PubMedCrossRefGoogle Scholar
  191. 191.
    Klaamas K, Kurtenkov O, von Mensdorff-Pouilly S, Shljapnikova L, Miljukhina L, Brjalin V, Lipping A (2007) Impact of Helicobacter pylori infection on the humoral immune response to MUC1 peptide in patients with chronic gastric diseases and gastric cancer. Immunol Invest 36:371–386PubMedCrossRefGoogle Scholar
  192. 192.
    Costa NR, Mendes N, Marcos NT, Reis CA, Caffrey T, Hollingsworth MA, Santos-Silva F (2008) Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells. World J Gastroenterol 14:1411–1414PubMedCentralPubMedCrossRefGoogle Scholar
  193. 193.
    Guang W, Ding H, Czinn SJ, Kim KC, Blanchard TG, Lillehoj EP (2010) Muc1 cell surface mucin attenuates epithelial inflammation in response to a common mucosal pathogen. J Biol Chem 285:20547–20557PubMedCentralPubMedCrossRefGoogle Scholar
  194. 194.
    Guang W, Twaddell WS, Lillehoj EP (2012) Molecular Interactions between MUC1 Epithelial Mucin, beta-Catenin, and CagA Proteins. Front Immunol 3:105PubMedCentralPubMedCrossRefGoogle Scholar
  195. 195.
    McAuley JL, Linden SK, Png CW, King RM, Pennington HL, Gendler SJ, Florin TH, Hill GR, Korolik V, McGuckin MA (2007) MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Investig 117:2313–2324PubMedCentralPubMedCrossRefGoogle Scholar
  196. 196.
    Linden SK, Florin TH, McGuckin MA (2008) Mucin dynamics in intestinal bacterial infection. PLoS One 3:e3952PubMedCentralPubMedCrossRefGoogle Scholar
  197. 197.
    Li X, Wang L, Nunes DP, Troxler RF, Offner GD (2003) Pro-inflammatory cytokines up-regulate MUC1 gene expression in oral epithelial cells. J Dent Res 82:883–887PubMedCrossRefGoogle Scholar
  198. 198.
    Tsuboi Y, Kim Y, Paparella MM, Chen N, Schachern PA, Lin J (2001) Pattern changes of mucin gene expression with pneumococcal otitis media. Int J Pediatr Otorhinolaryngol 61:23–30PubMedCrossRefGoogle Scholar
  199. 199.
    Kardon R, Price RE, Julian J, Lagow E, Tseng SC, Gendler SJ, Carson DD (1999) Bacterial conjunctivitis in Muc1 null mice. Invest Ophthalmol Vis Sci 40:1328–1335PubMedGoogle Scholar
  200. 200.
    Danjo Y, Hazlett LD, Gipson IK (2000) C57BL/6 mice lacking Muc1 show no ocular surface phenotype. Invest Ophthalmol Vis Sci 41:4080–4084PubMedGoogle Scholar
  201. 201.
    West RO (1966) Epidemiologic study of malignancies of the ovaries. Cancer 19:1001–1007PubMedCrossRefGoogle Scholar
  202. 202.
    Cramer DW, Vitonis AF, Pinheiro SP, McKolanis JR, Fichorova RN, Brown KE, Hatchette TF, Finn OJ (2010) Mumps and ovarian cancer: modern interpretation of an historic association. Cancer Causes Control 21:1193–1201PubMedCentralPubMedCrossRefGoogle Scholar
  203. 203.
    Buisine MP, Desreumaux P, Debailleul V, Gambiez L, Geboes K, Ectors N, Delescaut MP, Degand P, Aubert JP, Colombel JF, Porchet N (1999) Abnormalities in mucin gene expression in Crohn’s disease. Inflamm Bowel Dis 5:24–32PubMedCrossRefGoogle Scholar
  204. 204.
    Furr AE, Ranganathan S, Finn OJ (2010) Aberrant expression of MUC1 mucin in pediatric inflammatory bowel disease. Pediatr Dev Pathol 13:24–31PubMedCrossRefGoogle Scholar
  205. 205.
    Beatty PL, Narayanan S, Gariepy J, Ranganathan S, Finn OJ (2010) Vaccine against MUC1 antigen expressed in inflammatory bowel disease and cancer lessens colonic inflammation and prevents progression to colitis-associated colon cancer. Cancer Prev Res 3:438–446CrossRefGoogle Scholar
  206. 206.
    Nishida A, Lau CW, Zhang M, Andoh A, Shi HN, Mizoguchi E, Mizoguchi A (2012) The membrane-bound mucin Muc1 regulates T helper 17-cell responses and colitis in mice, Gastroenterology 142:865–874 (e862)Google Scholar
  207. 207.
    Hirasawa Y, Kohno N, Yokoyama A, Inoue Y, Abe M, Hiwada K (1997) KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts. Am J Respir Cell Mol Biol 17:501–507PubMedCrossRefGoogle Scholar
  208. 208.
    Dahiya R, Kwak KS, Ho SB, Yoon WH, Kim YS (1995) Cystic fibrosis and pancreatic cancer cells synthesize and secrete MUC1 type mucin gene product. Biochem Mol Biol Int 35:351–362PubMedGoogle Scholar
  209. 209.
    Ohshimo S, Bonella F, Grammann N, Starke K, Cui A, Bauer PC, Teschler H, Kohno N, Guzman J, Costabel U (2009) Serum KL-6 as a novel disease marker in adolescent and adult cystic fibrosis. Sarcoidosis vasculitis Diffus Lung Dis 26:47–53Google Scholar
  210. 210.
    Hayashi T, Ishida T, Motoya S, Itoh F, Takahashi T, Hinoda Y, Imai K (2001) Mucins and immune reactions to mucins in ulcerative colitis. Digestion 63(Suppl 1):28–31PubMedCrossRefGoogle Scholar
  211. 211.
    Sipaul F, Birchall M, Corfield A (2011) What role do mucins have in the development of laryngeal squamous cell carcinoma? A Syst Rev Eur Arch Oto-rhino-laryngol 268:1109–1117CrossRefGoogle Scholar
  212. 212.
    Paszkiewicz-Gadek A, Porowska H, Anchim T, Wolczynski S, Gindzienski A (2003) Biosynthesis of MUC1 mucin in human endometrial adenocarcinoma is modulated by estradiol and tamoxifen. Gynecol Endocrinol 17:37–44PubMedCrossRefGoogle Scholar
  213. 213.
    Smith RF, Stern BH, Smith AA (2008) Mucin immunohistochemistry in the diagnosis and mapping of extramammary Paget’s disease. J Cell Mol Med 12:1605–1610PubMedCentralPubMedCrossRefGoogle Scholar
  214. 214.
    Weissenbacher T, Kuhn C, Mayr D, Pavlik R, Friese K, Scholz C, Jeschke U, Ditsch N, Dian D (2011) Expression of mucin-1, galectin-1 and galectin-3 in human leiomyosarcoma in comparison to leiomyoma and myometrium. Anticancer Res 31:451–457PubMedGoogle Scholar
  215. 215.
    Brossart P, Schneider A, Dill P, Schammann T, Grunebach F, Wirths S, Kanz L, Buhring HJ, Brugger W (2001) The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. Cancer Res 61:6846–6850PubMedGoogle Scholar
  216. 216.
    Teruya-Feldstein J, Donnelly GB, Goy A, Hegde A, Nanjangud G, Qin J, Thaler H, Gilles F, Dyomin VG, Lloyd KO, Zelenetz AD, Houldsworth J, Chaganti RS (2003) MUC-1 mucin protein expression in B-cell lymphomas. Appl Immunohistochem Mole Morphol 11:28–32Google Scholar
  217. 217.
    Itzkowitz SH, Yuan M, Montgomery CK, Kjeldsen T, Takahashi HK, Bigbee WL, Kim YS (1989) Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. Cancer Res 49:197–204PubMedGoogle Scholar
  218. 218.
    Brockhausen I, Dowler T, Paulsen H (2009) Site directed processing: role of amino acid sequences and glycosylation of acceptor glycopeptides in the assembly of extended mucin type O-glycan core 2. Biochim Biophys Acta 1790:1244–1257PubMedCrossRefGoogle Scholar
  219. 219.
    Brockhausen I, Schachter H, Stanley P, O-GalNAc Glycans (2009) Essentials of Glycobiology. In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME (eds) Source Essentials of Glycobiology (Chap 9), 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor (NY)Google Scholar
  220. 220.
    von Mensdorff-Pouilly S, Petrakou E, Kenemans P, van Uffelen K, Verstraeten AA, Snijdewint FG, van Kamp GJ, Schol DJ, Reis CA, Price MR, Livingston PO, Hilgers J (2000) Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptide and n-acetylgalactosamine (GalNAc) peptides. Int J Cancer 86:702–712CrossRefGoogle Scholar
  221. 221.
    Karanikas V, Hwang L-A, Pearson J, Ong CS, Apostolopoulos V, Vaughan H, Xing PX, Jamieson G, Pietersz G, Tait B, Broadbent R, Thyme G, McKenzie IF (1997) Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein. J Clin Investig 100:2783–2792PubMedCentralPubMedCrossRefGoogle Scholar
  222. 222.
    Longenecker BM, Willans DJ, MacLean GD, Selvaraj S, Suresh MR, Noujaim AA (1987) Monoclonal antibodies and synthetic tumor-associated glycoconjugates in the study of the expression of Thomsen-Friedenreich-like and Tn-like antigens on human cancers. J Natl Cancer Inst 78:489–496PubMedGoogle Scholar
  223. 223.
    Itzkowitz SH, Bloom EJ, Kokal WA, Modin G, Hakomori S, Kim YS, Sialosyl-Tn (1990) A novel mucin antigen associated with prognosis in colorectal cancer patients. Cancer 66:1960–1966PubMedCrossRefGoogle Scholar
  224. 224.
    Kobayashi H, Terao T, Kawashima Y (1992) Serum sialyl Tn as an independent predictor of poor prognosis in patients with epithelial ovarian cancer. J Clin Oncol 10:95–101PubMedGoogle Scholar
  225. 225.
    Morse MA (2000) Technology evaluation: theratope, Biomira Inc. Curr Opin Mole Therapeutics 2:453–458Google Scholar
  226. 226.
    Thepharmaletter, Theratope Phase III results deliver blow to Merck KGaA and Biomira, http://www.thepharmaletter.com/file/31463/theratope-phase-iii-results-deliver-blow-to-merck-kgaa-and-biomira.html (2003)
  227. 227.
    Huang ZH, Shi L, Ma JW, Sun ZY, Cai H, Chen YX, Zhao YF, Li YM (2012) A totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine for cancer therapy. J Am Chem Soc 134:8730–8733PubMedCrossRefGoogle Scholar
  228. 228.
    Duffy MJ, Shering S, Sherry F, McDermott E, O’Higgins N (2000) CA 15-3: a prognostic marker in breast cancer. Int J Biol Markers 15:330–333PubMedGoogle Scholar
  229. 229.
    Ritts RE Jr, Del Villano BC, Go VL, Herberman RB, Klug TL, Zurawski VR Jr (1984) Initial clinical evaluation of an immunoradiometric assay for CA 19-9 using the NCI serum bank. Int J Cancer 33:339–345PubMedCrossRefGoogle Scholar
  230. 230.
    Jeschke U, Wiest I, Schumacher AL, Kupka M, Rack B, Stahn R, Karsten U, Mayr D, Friese K, Dian D (2012) Determination of MUC1 in sera of ovarian cancer patients and in sera of patients with benign changes of the ovaries with CA15-3, CA27.29, and PankoMab. Anticancer Res 32:2185–2189PubMedGoogle Scholar
  231. 231.
    Bray KR, Koda JE, Gaur PK (1987) Serum levels and biochemical characteristics of cancer-associated antigen CA-549, a circulating breast cancer marker. Cancer Res 47:5853–5860PubMedGoogle Scholar
  232. 232.
    Devine PL, Duroux MA, Quin RJ, McGuckin MA, Joy GJ, Ward BG, Pollard CW (1995) CA15-3, CASA, MSA, and TPS as diagnostic serum markers in breast cancer. Breast Cancer Res Treat 34:245–251PubMedCrossRefGoogle Scholar
  233. 233.
    Meisel M, Weise J, Schwesinger G, Straube W (1998) Cancer associated serum antigen (CASA) levels in patients with breast carcinoma and in 3 control groups without breast cancer. Arch Gynecol Obstet 261:159–162PubMedCrossRefGoogle Scholar
  234. 234.
    McGuckin MA, Layton GT, Bailey MJ, Hurst T, Khoo SK, Ward BG (1990) Evaluation of two new assays for tumor-associated antigens, CASA and OSA, found in the serum of patients with epithelial ovarian carcinoma–comparison with CA125. Gynecol Oncol 37:165–171PubMedCrossRefGoogle Scholar
  235. 235.
    Stacker SA, Sacks NP, Golder J, Tjandra JJ, Thompson CH, Smithyman A, McKenzie IF (1988) Evaluation of MSA as a serum marker in breast cancer: a comparison with CEA. Br J Cancer 57:298–303PubMedCentralPubMedCrossRefGoogle Scholar
  236. 236.
    Stacker SA, Thompson CH, Sacks NP, Tjandra J, Lowe MG, Bishop J, McKenzie IF (1988) Detection of mammary serum antigen in sera from breast cancer patients using monoclonal antibody 3E1.2. Cancer Res 48:7060–7066PubMedGoogle Scholar
  237. 237.
    Cooper EH, Forbes MA, Hancock AK, Price JJ, Parker D (1989) An evaluation of mucin-like carcinoma associated antigen (MCA) in breast cancer. Br J Cancer 59:797–800PubMedCentralPubMedCrossRefGoogle Scholar
  238. 238.
    Schecter RL, Major PP, Kovac PE, Ishida M, Kovalik EC, Dion AS, Langleben A, Boileau G, Boos G, Panasci L et al (1988) Double antibody radioimmunoassay for monitoring metastatic breast cancer. Br J Cancer 58:362–367PubMedCentralPubMedCrossRefGoogle Scholar
  239. 239.
    Tang CK, Apostolopoulos V (2008) Strategies used for MUC1 immunotherapy: preclinical studies. Expert Rev Vaccines 7:951–962PubMedCrossRefGoogle Scholar
  240. 240.
    Tang CK, Katsara M, Apostolopoulos V (2008) Strategies used for MUC1 immunotherapy: human clinical studies. Expert Rev Vaccines 7:963–975PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Vasso Apostolopoulos
    • 1
  • Lily Stojanovska
    • 1
  • Sharron E. Gargosky
    • 2
  1. 1.Centre for Chronic Disease, College of Health and BiomedicineVictoria UniversityMelbourneAustralia
  2. 2.Prima BioMed LtdSydneyAustralia

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