Association and Research Advancements of Clinical Application in Thomsen-Friedenreich Related Antigens and MUC1 Antigen_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Yang , CHENG Ruochuan

Treatment Center of Thyroid Disease， First Af?liated Hospital of Kunming Medical University， Kunming 650032， Yunnan Province， China;

Corresponding author：

Keywords：

Mucin 1; Tumor; Thomsen-Friedenreich related antigen

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Objective 　Mucin 1 （MUC1）and Thomsen-Friedenreich related antigens （TFRA）gene play an important role in the occurrence and development of tumor，so we will discuss its research advancements and clinical applications below.
Methods 　Foreign and native related literatures published in recent 10 years were retrieved，and a further exploration on the expression relationship and clinical research progression of MUC1 and TFRA were reviewed.
Results 　MUC1 and TFRA expressed in a high degree of specificity in malignant tumors，and their expressions interacted with each other. Many MUC1 related vaccines had been introduced to clinical in recent years，and some drugs based on TFRA had been put into clinical experiment as gene therapy methods too.
Conclusions 　MUC1 and TFRA may be used as new target antigens of specific immunotherapy for malignant tumor. That they express in high or low level is closely related to tumor biological behavior and prognosis， moreover， they are important to the diagnosis and treatment of cancer.

Citation： LI Yang,CHENG Ruochuan. Association and Research Advancements of Clinical Application in Thomsen-Friedenreich Related Antigens and MUC1 Antigen. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(10): 1136-1142. doi: Copy

1.	Apostolopoulos V， McKenzie IF. Cellular mucins：targets for　immunotherapy[J]. Crit Rev Immunol， 1994， 14(3-4)：293-309.
2.	Santos-Silva F， Fonseca A， Caffrey T， et al. Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism[J]. Glycobiology， 2005， 15(5)：511-517.
3.	Baldus SE， Hanisch FG， Kotlarek GM， et al. Coexpression of MUC1 mucin peptide core and the Thomsen-Friedenreich antigen in colorectal neoplasms[J]. Cancer， 1998， 82(6)：1019-1027.
4.	-galactosyltransferase (C1Gal-T2)，an enzyme synthesizing a core 1 structure of O-glycan[J]. J Biol Chem， 2002， 277(49)：47724-47731.
5.	Goletz S， Cao Y， Danielczyk A， et al. Thomsen-Friedenreich antigen：the “hidden” tumor antigen[J] . Adv Exp Med Biol， 2003， 535：147-162.
6.	Brockhausen I， Yang J， Lehotay M， et al. Pathways of mucin O-glycosylation in normal and malignant rat colonic epithelial cells reveal a mechanism for cancer-associated Sialyl-Tn antigen expression[J]. Biol Chem， 2001， 382(2)：219-232.
7.	Kudo T， Iwai T， Kubota T， et al. Molecular cloning and characterization of a novel UDP-Gal：GalNAc（alpha）peptide beta 1，.
8.	Dalziel M， Whitehouse C， McfarlaneⅠ， et al. The relativeactivities of the C2GnT1 and ST3Gal-I glycosyltransferasesdetermine O-glycan structure and expression of a tumor-associated epitope on MUC1[J]. J Biol Chem， 2001， 276(14)：11007-11015.
9.	Cao Y， Karsten UR， Liebrich W， et al. Expression of Thomsen-Friedenreich-related antigens in primary and metastatic colorectal carcinomas. A reevaluation[J]. Cancer， 1995， 76(10)：1700-1708.
10.	Baldus SE， Zirbes TK， Hanisch FG， et al. Thomsen-Friedenreichantigen presents as a prognostic factor in colorectal carcinoma：a clinicopathologic study of 264 patients[J]. Cancer， 2000， 88(7)：1536-1543.
11.	Cao Y， Merling A， Karsten U， et al. Expression of CD175（Tn）， CD175s（sialosyl-Tn）and CD176（Thomsen-Friedenreich antigen）on malignant human hematopoietic cells[J]. Int J Cancer， 2008， 123(1)：89-99.
12.	Lin WM， Karsten U， Goletz S， et al. Expression of CD176（Thomsen-Friedenreich antigen）on lung，breast and liver cancer-initiating cells[J]. Int J Exp Pathol， 2011， 92(2)：97-105.
13.	Lin WM， Karsten U， Goletz S， et al. Co-expression of CD173（H2）and CD174（Lewis Y）with CD44 suggests that fucosylated histo-blood group antigens are markers of breast cancer-initiating cells[J]. Virchows Arch， 2010， 456(4)：403-409.
14.	Jeschke U， Richter DU， Hammer A， et al. Expression of the Thomsen-Friedenreich antigen and of its putative carrier protein mucin 1 in the human placenta and in trophoblast cells in vitro[J]. Histochem Cell Biol， 2002， 117(3)：219-226.
15.	Avichezer D， Taylor-Papadimitriou J， Arnon R. A short synthetic peptide (DTRPAP) induces anti-mucin (MUC-1) antibody，which is reactive with human ovarian and breast cancer cells[J]. CancerBiochem Biophys， 1998， 16(1-2)：113-128.
16.	南方，何太平. BLP25脂质体疫苗治疗肺癌和前列腺癌的研究[J]. 国际生物制品学杂志， 2006， 29(5)：219-221.
17.	Butts C， Murray N， Maksymiuk A， et al. Randomized phaseⅡB trial of BLP25 liposome vaccine in stageⅢB and Ⅳnon-small-cell lung cancer[J]. J Clin Oncol， 2005， 23(27)：6674-6681.
18.	Sangha R， Butts C. L-BLP25：a peptide vaccine strategy in non small cell lung cancer[J]. Clin Cancer Res， 2007， 13(15 Pt 2)：S4652-S4654.
19.	Rong Y， Jin D， Wu W， et al. Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine[J]. BMC Cancer， 2009， 9(1)：191.
20.	Danielczyk A， Stahn R， Faulstich D， et al. PankoMab：a potent new generation anti-tumour MUC1 antibody[J]. Cancer Immunol Immunother， 2006， 55(11)：1337-1347.
21.	Takanami I. Expression of Thomsen-Friedenreich antigen as a marker of poor prognosis in pulmonary adenocarcinoma[J]. Oncol Rep， 1999， 6(2)：341-344.
22.	Landon LA， Peletskaya EN， Glinsky VV， et al. Combinatorial evolution of high-affinity peptides that bind to the Thomsen-Friedenreich carcinoma antigen[J]. J Protein Chem， 2003， 22(2)：193-204.
23.	Hoffmann-Röder A， Kaiser A， Wagner S， et al. Synthetic antitumor vaccines from tetanus toxoid conjugates of MUC1 glycopeptides with the Thomsen-Friedenreich antigen and a fluorine-substituted analogue[J]. Angew Chem Int Ed Engl， 2010， 49(45)：8498-8503.
24.	Ashida H， Yamamoto K， Kumagai H. Enzymatic syntheses ofT antigen-containing glycolipid mimicry using the transglycosylationactivity of endo-alpha-N-acetylgalactosaminidase[J]. Carbohydr Res， 2001， 330(4)：487-493.
25.	易濒，张敏，曹毅. Thomsen-Friedenreich 抗原（TF，CD176）抗体诱导人类白血病细胞凋亡的机制研究[C]. “细胞活动生命活力”中国细胞生物学学会全体会员代表大会暨第十二次学术大会，北京， 2011.
26.	Coats MT， Murphy T， Paton JC， et al. Exposure of Thomsen-Friedenreich antigen in streptococcus pneumoniae infection isdependent on pneumococcal neuraminidase A[J]. Microb Pathog，.
27.	Springer GF. Immunoreactive T and Tn epitopes in cancer diagnosis，prognosis，and immunotherapy[J]. J Mol Med， 1997， 75(8)：594-602.
28.	Imai J， Ghazizadeh M， Naito Z， et al. Immunohistochemical expression of T，Tn and sialyl-Tn antigens and clinical outcome in human breast carcinoma[J]. Anticancer Res， 2001， 21(2B)：1327-1334.
29.	Schindlbeck C， Jeschke U， Schulze S， et al. Prognostic impact of Thomsen-Friedenreich tumor antigen and disseminated tumor cells in the bone marrow of breast cancer patients[J]. Breast Cancer Res Treat， 2007， 101(1)：17-25.
30.	Smorodin EP， Kurtenkov OA， Sergeyev BL， et al. Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level：the follow-up study of gastrointestinal cancer patients[J]. World J Gastroenterol， 2008， 14(27)：4352-4358.
31.	Poiroux G， Pitié M， Culerrier R， et al. Morniga G：a plant lectin　as an endocytic ligand for photosensitizer molecule targeting　toward tumor-associated T/Tn antigens[J]. Photochem Photobiol， 2011， 87(2)：370-377.
32.	Poiroux G， Pitié M， Culerrier R， et al. Targeting of T/Tn antigens　with a plant lectin to kill human leukemia cells by photochemotherapy[J]. PLoS One， 2011， 6(8)：e23315.
33.	， 50(6)：343-349.

1. Apostolopoulos V， McKenzie IF. Cellular mucins：targets for　immunotherapy[J]. Crit Rev Immunol， 1994， 14(3-4)：293-309.
2. Santos-Silva F， Fonseca A， Caffrey T， et al. Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism[J]. Glycobiology， 2005， 15(5)：511-517.
3. Baldus SE， Hanisch FG， Kotlarek GM， et al. Coexpression of MUC1 mucin peptide core and the Thomsen-Friedenreich antigen in colorectal neoplasms[J]. Cancer， 1998， 82(6)：1019-1027.
4. -galactosyltransferase (C1Gal-T2)，an enzyme synthesizing a core 1 structure of O-glycan[J]. J Biol Chem， 2002， 277(49)：47724-47731.
5. Goletz S， Cao Y， Danielczyk A， et al. Thomsen-Friedenreich antigen：the “hidden” tumor antigen[J] . Adv Exp Med Biol， 2003， 535：147-162.
6. Brockhausen I， Yang J， Lehotay M， et al. Pathways of mucin O-glycosylation in normal and malignant rat colonic epithelial cells reveal a mechanism for cancer-associated Sialyl-Tn antigen expression[J]. Biol Chem， 2001， 382(2)：219-232.
7. Kudo T， Iwai T， Kubota T， et al. Molecular cloning and characterization of a novel UDP-Gal：GalNAc（alpha）peptide beta 1，.
8. Dalziel M， Whitehouse C， McfarlaneⅠ， et al. The relativeactivities of the C2GnT1 and ST3Gal-I glycosyltransferasesdetermine O-glycan structure and expression of a tumor-associated epitope on MUC1[J]. J Biol Chem， 2001， 276(14)：11007-11015.
9. Cao Y， Karsten UR， Liebrich W， et al. Expression of Thomsen-Friedenreich-related antigens in primary and metastatic colorectal carcinomas. A reevaluation[J]. Cancer， 1995， 76(10)：1700-1708.
10. Baldus SE， Zirbes TK， Hanisch FG， et al. Thomsen-Friedenreichantigen presents as a prognostic factor in colorectal carcinoma：a clinicopathologic study of 264 patients[J]. Cancer， 2000， 88(7)：1536-1543.
11. Cao Y， Merling A， Karsten U， et al. Expression of CD175（Tn）， CD175s（sialosyl-Tn）and CD176（Thomsen-Friedenreich antigen）on malignant human hematopoietic cells[J]. Int J Cancer， 2008， 123(1)：89-99.
12. Lin WM， Karsten U， Goletz S， et al. Expression of CD176（Thomsen-Friedenreich antigen）on lung，breast and liver cancer-initiating cells[J]. Int J Exp Pathol， 2011， 92(2)：97-105.
13. Lin WM， Karsten U， Goletz S， et al. Co-expression of CD173（H2）and CD174（Lewis Y）with CD44 suggests that fucosylated histo-blood group antigens are markers of breast cancer-initiating cells[J]. Virchows Arch， 2010， 456(4)：403-409.
14. Jeschke U， Richter DU， Hammer A， et al. Expression of the Thomsen-Friedenreich antigen and of its putative carrier protein mucin 1 in the human placenta and in trophoblast cells in vitro[J]. Histochem Cell Biol， 2002， 117(3)：219-226.
15. Avichezer D， Taylor-Papadimitriou J， Arnon R. A short synthetic peptide (DTRPAP) induces anti-mucin (MUC-1) antibody，which is reactive with human ovarian and breast cancer cells[J]. CancerBiochem Biophys， 1998， 16(1-2)：113-128.
16. 南方，何太平. BLP25脂质体疫苗治疗肺癌和前列腺癌的研究[J]. 国际生物制品学杂志， 2006， 29(5)：219-221.
17. Butts C， Murray N， Maksymiuk A， et al. Randomized phaseⅡB trial of BLP25 liposome vaccine in stageⅢB and Ⅳnon-small-cell lung cancer[J]. J Clin Oncol， 2005， 23(27)：6674-6681.
18. Sangha R， Butts C. L-BLP25：a peptide vaccine strategy in non small cell lung cancer[J]. Clin Cancer Res， 2007， 13(15 Pt 2)：S4652-S4654.
19. Rong Y， Jin D， Wu W， et al. Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine[J]. BMC Cancer， 2009， 9(1)：191.
20. Danielczyk A， Stahn R， Faulstich D， et al. PankoMab：a potent new generation anti-tumour MUC1 antibody[J]. Cancer Immunol Immunother， 2006， 55(11)：1337-1347.
21. Takanami I. Expression of Thomsen-Friedenreich antigen as a marker of poor prognosis in pulmonary adenocarcinoma[J]. Oncol Rep， 1999， 6(2)：341-344.
22. Landon LA， Peletskaya EN， Glinsky VV， et al. Combinatorial evolution of high-affinity peptides that bind to the Thomsen-Friedenreich carcinoma antigen[J]. J Protein Chem， 2003， 22(2)：193-204.
23. Hoffmann-Röder A， Kaiser A， Wagner S， et al. Synthetic antitumor vaccines from tetanus toxoid conjugates of MUC1 glycopeptides with the Thomsen-Friedenreich antigen and a fluorine-substituted analogue[J]. Angew Chem Int Ed Engl， 2010， 49(45)：8498-8503.
24. Ashida H， Yamamoto K， Kumagai H. Enzymatic syntheses ofT antigen-containing glycolipid mimicry using the transglycosylationactivity of endo-alpha-N-acetylgalactosaminidase[J]. Carbohydr Res， 2001， 330(4)：487-493.
25. 易濒，张敏，曹毅. Thomsen-Friedenreich 抗原（TF，CD176）抗体诱导人类白血病细胞凋亡的机制研究[C]. “细胞活动生命活力”中国细胞生物学学会全体会员代表大会暨第十二次学术大会，北京， 2011.
26. Coats MT， Murphy T， Paton JC， et al. Exposure of Thomsen-Friedenreich antigen in streptococcus pneumoniae infection isdependent on pneumococcal neuraminidase A[J]. Microb Pathog，.
27. Springer GF. Immunoreactive T and Tn epitopes in cancer diagnosis，prognosis，and immunotherapy[J]. J Mol Med， 1997， 75(8)：594-602.
28. Imai J， Ghazizadeh M， Naito Z， et al. Immunohistochemical expression of T，Tn and sialyl-Tn antigens and clinical outcome in human breast carcinoma[J]. Anticancer Res， 2001， 21(2B)：1327-1334.
29. Schindlbeck C， Jeschke U， Schulze S， et al. Prognostic impact of Thomsen-Friedenreich tumor antigen and disseminated tumor cells in the bone marrow of breast cancer patients[J]. Breast Cancer Res Treat， 2007， 101(1)：17-25.
30. Smorodin EP， Kurtenkov OA， Sergeyev BL， et al. Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level：the follow-up study of gastrointestinal cancer patients[J]. World J Gastroenterol， 2008， 14(27)：4352-4358.
31. Poiroux G， Pitié M， Culerrier R， et al. Morniga G：a plant lectin　as an endocytic ligand for photosensitizer molecule targeting　toward tumor-associated T/Tn antigens[J]. Photochem Photobiol， 2011， 87(2)：370-377.
32. Poiroux G， Pitié M， Culerrier R， et al. Targeting of T/Tn antigens　with a plant lectin to kill human leukemia cells by photochemotherapy[J]. PLoS One， 2011， 6(8)：e23315.
33. ， 50(6)：343-349.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Association and Research Advancements of Clinical Application in Thomsen-Friedenreich Related Antigens and MUC1 Antigen

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