• 云南省昆明醫(yī)科大學(xué)第一附屬醫(yī)院甲狀腺診療中心(云南昆明 650032);

目的  黏蛋白1與TF相關(guān)抗原基因都是與腫瘤的發(fā)生和發(fā)展有密切關(guān)系的基因,對(duì)其基因及蛋白質(zhì)在國內(nèi)外的研究進(jìn)展與臨床應(yīng)用進(jìn)行探討和展望。
方法  回顧性總結(jié)國內(nèi)外近10年的文獻(xiàn),對(duì)黏蛋白1與TF相關(guān)抗原的表達(dá)關(guān)系及臨床研究進(jìn)展進(jìn)行討論。
結(jié)果  黏蛋白1與TF相關(guān)抗原在腫瘤的表達(dá)中存在高度的特異性,且二者存在共表達(dá)并相互影響。與黏蛋白1相關(guān)的多種疫苗已經(jīng)投入臨床使用,部分基于TF相關(guān)抗原的藥物也已進(jìn)入臨床試驗(yàn)階段。
結(jié)論  黏蛋白1與TF相關(guān)抗原可作為腫瘤治療的新型靶抗原,其表達(dá)與腫瘤的生物學(xué)行為與預(yù)后密切相關(guān),對(duì)腫瘤的診斷和治療有重要意義。

引用本文: 李洋,程若川. TF相關(guān)抗原與MUC1的相關(guān)性和臨床應(yīng)用研究進(jìn)展. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(10): 1136-1142. doi: 復(fù)制

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脂質(zhì)體疫苗治療肺癌和前列腺癌的研究[J]. 國際生物制品學(xué)雜志, 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. 易瀕, 張敏, 曹毅. Thomsen-Friedenreich 抗原(TF,CD176)抗體誘導(dǎo)人類白血病細(xì)胞凋亡的機(jī)制研究[C]. “細(xì)胞活動(dòng) 生命活力”中國細(xì)胞生物學(xué)學(xué)會(huì)全體會(huì)員代表大會(huì)暨第十二次學(xué)術(shù)大會(huì), 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. 1. Apostolopoulos V, McKenzie IF. Cellular mucins:targets for immunotherapy[J]. Crit Rev Immunol, 1994, 14(3-4):293-309.
  2. 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. 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. 4. -galactosyltransferase (C1Gal-T2),an enzyme synthesizing a core 1 structure of O-glycan[J]. J Biol Chem, 2002, 277(49):47724-47731.
  5. 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. 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. 7. Kudo T, Iwai T, Kubota T, et al. Molecular cloning and characterization of a novel UDP-Gal:GalNAc(alpha)peptide beta 1,.
  8. 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. 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. 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. 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. 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. 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. 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. 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. 16. 南方, 何太平. BLP25脂質(zhì)體疫苗治療肺癌和前列腺癌的研究[J]. 國際生物制品學(xué)雜志, 2006, 29(5):219-221.
  17. 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. 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. 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. 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. 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. 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. 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. 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. 25. 易瀕, 張敏, 曹毅. Thomsen-Friedenreich 抗原(TF,CD176)抗體誘導(dǎo)人類白血病細(xì)胞凋亡的機(jī)制研究[C]. “細(xì)胞活動(dòng) 生命活力”中國細(xì)胞生物學(xué)學(xué)會(huì)全體會(huì)員代表大會(huì)暨第十二次學(xué)術(shù)大會(huì), 北京, 2011.
  26. 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. 27. Springer GF. Immunoreactive T and Tn epitopes in cancer diagnosis,prognosis,and immunotherapy[J]. J Mol Med, 1997, 75(8):594-602.
  28. 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. 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. 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. 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. 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. 33. , 50(6):343-349.