The Role of Sialyl-Tn in Cancer
Abstract
:1. Introduction
2. Synthesis of the Sialyl-Tn (sTn) Antigen
3. sTn Is an Onco-Foetal Antigen
4. sTn as a Prognostic Biomarker
5. The Role of sTn in Cancer Progression
6. Future Perspectives
Acknowledgments
Conflicts of Interest
References
- Pinho, S.S.; Reis, C.A. Glycosylation in cancer: Mechanisms and clinical implications. Nat. Rev. Cancer 2015, 15, 540–555. [Google Scholar] [CrossRef] [PubMed]
- Kim, Y.J.; Varki, A. Perspectives on the significance of altered glycosylation of glycoproteins in cancer. Glycoconj. J. 1997, 14, 569–576. [Google Scholar] [CrossRef] [PubMed]
- Tarp, M.A.; Clausen, H. Mucin-type O-glycosylation and its potential use in drug and vaccine development. Biochim. Biophys. Acta 2008, 1780, 546–563. [Google Scholar] [CrossRef] [PubMed]
- Brockhausen, I.; Yang, J.; Dickinson, N.; Ogata, S.; Itzkowitz, S.H. Enzymatic basis for sialyl-Tn expression in human colon cancer cells. Glycoconj. J. 1998, 15, 595–603. [Google Scholar] [CrossRef] [PubMed]
- Ohuchi, N.; Thor, A.; Nose, M.; Fujita, J.; Kyogoku, M.; Schlom, J. Tumor-associated glycoprotein (TAG-72) detected in adenocarcinomas and benign lesions of the stomach. Int. J. Cancer 1986, 38, 643–650. [Google Scholar] [CrossRef] [PubMed]
- Itzkowitz, S.H.; Yuan, M.; Montgomery, C.K.; Kjeldsen, T.; Takahashi, H.K.; Bigbee, W.L.; Kim, Y.S. Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. Cancer Res. 1989, 49, 197–204. [Google Scholar] [PubMed]
- Thor, A.; Ohuchi, N.; Szpak, C.A.; Johnston, W.W.; Schlom, J. Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3. Cancer Res. 1986, 46, 3118–3124. [Google Scholar] [PubMed]
- Lottich, S.C.; Johnston, W.W.; Szpak, C.A.; Delong, E.R.; Thor, A.; Schlom, J. Tumor-associated antigen TAG-72: Correlation of expression in primary and metastatic breast carcinoma lesions. Breast Cancer Res. Treat. 1985, 6, 49–56. [Google Scholar] [CrossRef] [PubMed]
- Johnston, W.W.; Szpak, C.A.; Thor, A.; Schlom, J. Phenotypic characterization of lung cancers in fine needle aspiration biopsies using monoclonal antibody B72.3. Cancer Res. 1986, 46, 6462–6470. [Google Scholar] [PubMed]
- Flucke, U.; Zirbes, T.K.; Schroder, W.; Monig, S.P.; Koch, V.; Schmitz, K.; Thiele, J.; Dienes, H.P.; Holscher, A.H.; Baldus, S.E. Expression of mucin-associated carbohydrate core antigens in esophageal squamous cell carcinomas. Anticancer Res. 2001, 21, 2189–2193. [Google Scholar] [PubMed]
- Ching, C.K.; Holmes, S.W.; Holmes, G.K.; Long, R.G. Comparison of two sialosyl-Tn binding monoclonal antibodies (MLS102 and B72.3) in detecting pancreatic cancer. Gut 1993, 34, 1722–1725. [Google Scholar] [CrossRef] [PubMed]
- Genega, E.M.; Hutchinson, B.; Reuter, V.E.; Gaudin, P.B. Immunophenotype of high-grade prostatic adenocarcinoma and urothelial carcinoma. Modern Pathol. 2000, 13, 1186–1191. [Google Scholar] [CrossRef] [PubMed]
- Myers, R.B.; Meredith, R.F.; Schlom, J.; LoBuglio, A.F.; Bueschen, A.J.; Wheeler, R.H.; Stockard, C.R.; Grizzle, W.E. Tumor associated glycoprotein-72 is highly expressed in prostatic adenocarcinomas. J. Urol. 1994, 152, 243–246. [Google Scholar] [PubMed]
- Ferreira, J.A.; Videira, P.A.; Lima, L.; Pereira, S.; Silva, M.; Carrascal, M.; Severino, P.F.; Fernandes, E.; Almeida, A.; Costa, C.; et al. Overexpression of tumour-associated carbohydrate antigen sialyl-Tn in advanced bladder tumours. Mol. Oncol. 2013, 7, 719–731. [Google Scholar] [CrossRef] [PubMed]
- Hashiguchi, Y.; Kasai, M.; Fukuda, T.; Ichimura, T.; Yasui, T.; Sumi, T. Serum sialyl-Tn (sTn) as a tumor marker in patients with endometrial cancer. Pathol. Oncol. Res. POR 2015. [Google Scholar] [CrossRef] [PubMed]
- Julien, S.; Videira, P.A.; Delannoy, P. Sialyl-Tn in cancer: (How) did we miss the target? Biomolecules 2012, 2, 435–466. [Google Scholar] [CrossRef] [PubMed]
- Sewell, R.; Backstrom, M.; Dalziel, M.; Gschmeissner, S.; Karlsson, H.; Noll, T.; Gatgens, J.; Clausen, H.; Hansson, G.C.; Burchell, J.; et al. The ST6GalNAc-I sialyltransferase localizes throughout the Golgi and is responsible for the synthesis of the tumor-associated sialyl-Tn O-glycan in human breast cancer. J. Biol. Chem. 2006, 281, 3586–3594. [Google Scholar] [CrossRef] [PubMed]
- Ju, T.; Lanneau, G.S.; Gautam, T.; Wang, Y.; Xia, B.; Stowell, S.R.; Willard, M.T.; Wang, W.; Xia, J.Y.; Zuna, R.E.; et al. Human tumor antigens Tn and sialyl Tn arise from mutations in COSMC. Cancer Res. 2008, 68, 1636–1646. [Google Scholar] [CrossRef] [PubMed]
- Radhakrishnan, P.; Dabelsteen, S.; Madsen, F.B.; Francavilla, C.; Kopp, K.L.; Steentoft, C.; Vakhrushev, S.Y.; Olsen, J.V.; Hansen, L.; Bennett, E.P.; et al. Immature truncated O-glycophenotype of cancer directly induces oncogenic features. Proc. Natl. Acad. Sci. USA 2014, 111, E4066–E4075. [Google Scholar] [CrossRef] [PubMed]
- Gill, D.J.; Chia, J.; Senewiratne, J.; Bard, F. Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes. J. Cell Biol. 2010, 189, 843–858. [Google Scholar] [CrossRef] [PubMed]
- Hassinen, A.; Pujol, F.M.; Kokkonen, N.; Pieters, C.; Kihlstrom, M.; Korhonen, K.; Kellokumpu, S. Functional organization of Golgi N- and O-glycosylation pathways involves pH-dependent complex formation that is impaired in cancer cells. J. Biol. Chem. 2011, 286, 38329–38340. [Google Scholar] [CrossRef] [PubMed]
- Marcos, N.T.; Bennett, E.P.; Gomes, J.; Magalhaes, A.; Gomes, C.; David, L.; Dar, I.; Jeanneau, C.; DeFrees, S.; Krustrup, D.; et al. ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues. Front. Biosci. 2011, 3, 1443–1455. [Google Scholar] [CrossRef]
- Harduin-Lepers, A.; Vallejo-Ruiz, V.; Krzewinski-Recchi, M.A.; Samyn-Petit, B.; Julien, S.; Delannoy, P. The human sialyltransferase family. Biochimie 2001, 83, 727–737. [Google Scholar] [CrossRef]
- Julien, S.; Adriaenssens, E.; Ottenberg, K.; Furlan, A.; Courtand, G.; Vercoutter-Edouart, A.S.; Hanisch, F.G.; Delannoy, P.; Le Bourhis, X. ST6GalNAc I expression in MDA-MB-231 breast cancer cells greatly modifies their O-glycosylation pattern and enhances their tumourigenicity. Glycobiology 2006, 16, 54–64. [Google Scholar] [CrossRef] [PubMed]
- Munkley, J.; Oltean, S.; Vodak, D.; Wilson, B.T.; Livermore, K.E.; Zhou, Y.; Star, E.; Floros, V.I.; Johannessen, B.; Knight, B.; et al. The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer. Oncotarget 2015, 6, 34358–34374. [Google Scholar] [PubMed]
- Marcos, N.T.; Pinho, S.; Grandela, C.; Cruz, A.; Samyn-Petit, B.; Harduin-Lepers, A.; Almeida, R.; Silva, F.; Morais, V.; Costa, J.; et al. Role of the human ST6GalNAc-I and ST6GalNAc-II in the synthesis of the cancer-associated sialyl-Tn antigen. Cancer Res. 2004, 64, 7050–7057. [Google Scholar] [CrossRef] [PubMed]
- Ju, T.; Aryal, R.P.; Stowell, C.J.; Cummings, R.D. Regulation of protein O-glycosylation by the endoplasmic reticulum-localized molecular chaperone COSMC. J. Cell Biol. 2008, 182, 531–542. [Google Scholar] [CrossRef] [PubMed]
- Ju, T.; Cummings, R.D. A unique molecular chaperone COSMC required for activity of the mammalian core 1 β3-galactosyltransferase. Proc. Natl. Acad. Sci. USA 2002, 99, 16613–16618. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Ju, T.; Ding, X.; Xia, B.; Wang, W.; Xia, L.; He, M.; Cummings, R.D. COSMC is an essential chaperone for correct protein O-glycosylation. Proc. Natl. Acad. Sci. USA 2010, 107, 9228–9233. [Google Scholar] [CrossRef] [PubMed]
- Yoo, N.J.; Kim, M.S.; Lee, S.H. Absence of COSMC gene mutations in breast and colorectal carcinomas. APMIS 2008, 116, 154–155. [Google Scholar] [CrossRef] [PubMed]
- Stanick, D.; Schuss, A.; Mishriki, Y.; Chao, S.; Thor, A.; Lundy, J. Reactivity of the monoclonal antibody B72.3 with fetal antigen: Correlation with expression of TAG-72 in human carcinomas. Cancer Investig. 1988, 6, 279–287. [Google Scholar] [CrossRef]
- Pistolesi, S.; Nuti, M.; Castagna, M.; Pingitore, R. Mammary fetal gland: Identification of new oncofetal antigens by monoclonal antibodies B72.3, MM1.80 and 4.36. Tumori 2001, 87, 252–255. [Google Scholar] [PubMed]
- Baldus, S.E.; Hanisch, F.G.; Schwonzen, M.; Nakahara, Y.; Iijima, H.; Ogawa, T.; Peter-Katalinic, J.; Uhlenbruck, G. Monoclonal antibody SP-21 defines a sialosyl-Tn antigen expressed on carcinomas and K562 erythroleukemia cells. Anticancer Res. 1992, 12, 1935–1940. [Google Scholar] [PubMed]
- Cao, Y.; Stosiek, P.; Springer, G.F.; Karsten, U. Thomsen-friedenreich-related carbohydrate antigens in normal adult human tissues: A systematic and comparative study. Histochem. Cell Biol. 1996, 106, 197–207. [Google Scholar] [CrossRef] [PubMed]
- Itoh, T.; Yonezawa, S.; Nomoto, M.; Ueno, K.; Kim, Y.S.; Sato, E. Expression of mucin antigens and lewis X-related antigens in carcinomas and dysplasia of the pharynx and larynx. Pathol. Int. 1996, 46, 646–655. [Google Scholar] [CrossRef] [PubMed]
- Ta, A.; Harpaz, N.; Bodian, C.; Roston, A.; Oberman, L.; Chen, A.; Itzkowitz, S. Sialyl-Tn antigen expression in Crohn’s colitis. Inflamm. Bowel Dis. 1997, 3, 254–259. [Google Scholar] [CrossRef] [PubMed]
- Barresi, G.; Giuffre, G.; Vitarelli, E.; Grosso, M.; Tuccari, G. The immunoexpression of Tn, sialyl-Tn and T antigens in chronic active gastritis in relation to helicobacter pylori infection. Pathology 2001, 33, 298–302. [Google Scholar] [PubMed]
- Cohen, M.; Drut, R.; Cueto Rua, E. Sialyl-Tn antigen distribution in helicobacter pylori chronic gastritis in children: An immunohistochemical study. Pediatr. Pathol. Mol. Med. 2003, 22, 117–129. [Google Scholar] [CrossRef] [PubMed]
- Federici, M.F.; Kudryashov, V.; Saigo, P.E.; Finstad, C.L.; Lloyd, K.O. Selection of carbohydrate antigens in human epithelial ovarian cancers as targets for immunotherapy: Serous and mucinous tumors exhibit distinctive patterns of expression. Int. J. Cancer 1999, 81, 193–198. [Google Scholar] [CrossRef]
- Pinto, R.; Carvalho, A.S.; Conze, T.; Magalhaes, A.; Picco, G.; Burchell, J.M.; Taylor-Papadimitriou, J.; Reis, C.A.; Almeida, R.; Mandel, U.; et al. Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation. J. Cell. Mol. Med. 2012, 16, 1474–1484. [Google Scholar] [CrossRef] [PubMed]
- Lopez-Ferrer, A.; Barranco, C.; de Bolos, C. Differences in the O-glycosylation patterns between lung squamous cell carcinoma and adenocarcinoma. Am. J. Clin. Pathol. 2002, 118, 749–755. [Google Scholar] [CrossRef] [PubMed]
- Ozaki, H.; Matsuzaki, H.; Ando, H.; Kaji, H.; Nakanishi, H.; Ikehara, Y.; Narimatsu, H. Enhancement of metastatic ability by ectopic expression of ST6GalNAcI on a gastric cancer cell line in a mouse model. Clin. Exp. Metastasis 2012, 29, 229–238. [Google Scholar] [CrossRef] [PubMed]
- Clement, M.; Rocher, J.; Loirand, G.; Le Pendu, J. Expression of sialyl-Tn epitopes on β1 integrin alters epithelial cell phenotype, proliferation and haptotaxis. J. Cell Sci. 2004, 117, 5059–5069. [Google Scholar] [CrossRef] [PubMed]
- Julien, S.; Picco, G.; Sewell, R.; Vercoutter-Edouart, A.S.; Tarp, M.; Miles, D.; Taylor-Papadimitriou, J.; Clausen, H.; Burchell, J.M. Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model. Br. J. Cancer 2009, 100, 1746–1754. [Google Scholar] [CrossRef] [PubMed]
- Schultz, M.J.; Swindall, A.F.; Bellis, S.L. Regulation of the metastatic cell phenotype by sialylated glycans. Cancer Metastasis Rev. 2012, 31, 501–518. [Google Scholar] [CrossRef] [PubMed]
- Takahashi, I.; Maehara, Y.; Kusumoto, T.; Yoshida, M.; Kakeji, Y.; Kusumoto, H.; Furusawa, M.; Sugimachi, K. Predictive value of preoperative serum sialyl Tn antigen levels in prognosis of patients with gastric cancer. Cancer 1993, 72, 1836–1840. [Google Scholar] [CrossRef]
- Nakagoe, T.; Sawai, T.; Tsuji, T.; Jibiki, M.A.; Nanashima, A.; Yamaguchi, H.; Yasutake, T.; Ayabe, H.; Arisawa, K.; Ishikawa, H. Predictive factors for preoperative serum levels of sialy lewis(x), sialyl lewis(a) and sialyl Tn antigens in gastric cancer patients. Anticancer Res. 2002, 22, 451–458. [Google Scholar] [PubMed]
- Motoo, Y.; Kawakami, H.; Watanabe, H.; Satomura, Y.; Ohta, H.; Okai, T.; Makino, H.; Toya, D.; Sawabu, N. Serum sialyl-Tn antigen levels in patients with digestive cancers. Oncology 1991, 48, 321–326. [Google Scholar] [CrossRef] [PubMed]
- Sato, T.; Nishimura, G.; Nonomura, A.; Miwa, K.; Miyazaki, I. Serological studies on CEA, CA 19–9, sTn and SLX in colorectal cancer. Hepatogastroenterology 1999, 46, 914–919. [Google Scholar] [PubMed]
- Nanashima, A.; Yamaguchi, H.; Nakagoe, T.; Matsuo, S.; Sumida, Y.; Tsuji, T.; Sawai, T.; Yamaguchi, E.; Yasutake, T.; Ayabe, H. High serum concentrations of sialyl Tn antigen in carcinomas of the biliary tract and pancreas. J. Hepato-Biliary-Pancreat. Surg. 1999, 6, 391–395. [Google Scholar] [CrossRef]
- Numa, F.; Tsunaga, N.; Michioka, T.; Nawata, S.; Ogata, H.; Kato, H. Tissue expression of sialyl Tn antigen in gynecologic tumors. J. Obstet. Gynaecol. 1995, 21, 385–389. [Google Scholar] [CrossRef]
- Kobayashi, H.; Terao, T.; Kawashima, Y. Sialyl Tn as a prognostic marker in epithelial ovarian cancer. Br. J. Cancer 1992, 66, 984–985. [Google Scholar] [CrossRef] [PubMed]
- Inoue, M.; Ogawa, H.; Nakanishi, K.; Tanizawa, O.; Karino, K.; Endo, J. Clinical value of sialyl Tn antigen in patients with gynecologic tumors. Obstet. Gynecol. 1990, 75, 1032–1036. [Google Scholar] [PubMed]
- Imada, T.; Rino, Y.; Takahashi, M.; Hatori, S.; Shiozawa, M.; Amano, T.; Kondo, J. Serum CA 19–9, SLX, sTn and CEA levels of the peripheral and the draining venous blood in gastric cancer. Hepatogastroenterology 1999, 46, 2086–2090. [Google Scholar] [PubMed]
- Arai, T.; Fujita, K.; Fujime, M.; Irimura, T. Expression of sialylated muc1 in prostate cancer: Relationship to clinical stage and prognosis. Int. J. Urol. 2005, 12, 654–661. [Google Scholar] [CrossRef] [PubMed]
- D’Amico, T.A.; Aloia, T.A.; Moore, M.B.; Herndon, J.E., II; Brooks, K.R.; Lau, C.L.; Harpole, D.H., Jr. Molecular biologic substaging of stage i lung cancer according to gender and histology. Ann. Thorac. Surg. 2000, 69, 882–886. [Google Scholar]
- Itzkowitz, S.; Kjeldsen, T.; Friera, A.; Hakomori, S.; Yang, U.S.; Kim, Y.S. Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Gastroenterology 1991, 100, 1691–1700. [Google Scholar] [PubMed]
- Kim, G.E.; Bae, H.I.; Park, H.U.; Kuan, S.F.; Crawley, S.C.; Ho, J.J.; Kim, Y.S. Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. Gastroenterology 2002, 123, 1052–1060. [Google Scholar] [CrossRef] [PubMed]
- Davidson, B.; Berner, A.; Nesland, J.M.; Risberg, B.; Kristensen, G.B.; Trope, C.G.; Bryne, M. Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous effusions from patients diagnosed with epithelial ovarian carcinoma: Evidence of up-regulated Tn and sialyl Tn antigen expression in effusions. Hum. Pathol. 2000, 31, 1081–1087. [Google Scholar] [CrossRef] [PubMed]
- Davidson, B.; Gotlieb, W.H.; Ben-Baruch, G.; Kopolovic, J.; Goldberg, I.; Nesland, J.M.; Berner, A.; Bjamer, A.; Bryne, M. Expression of carbohydrate antigens in advanced-stage ovarian carcinomas and their metastases—A clinicopathologic study. Gynecol. Oncol. 2000, 77, 35–43. [Google Scholar] [CrossRef] [PubMed]
- Schmitt, F.C.; Figueiredo, P.; Lacerda, M. Simple mucin-type carbohydrate antigens (T, sialosyl-T, Tn and sialosyl-Tn) in breast carcinogenesis. Virchows Arch. 1995, 427, 251–258. [Google Scholar] [CrossRef] [PubMed]
- Ogata, S.; Maimonis, P.J.; Itzkowitz, S.H. Mucins bearing the cancer-associated sialosyl-Tn antigen mediate inhibition of natural killer cell cytotoxicity. Cancer Res. 1992, 52, 4741–4746. [Google Scholar] [PubMed]
- Hauselmann, I.; Borsig, L. Altered tumor-cell glycosylation promotes metastasis. Front. Oncol. 2014, 4. [Google Scholar] [CrossRef] [PubMed]
- Munkley, J.; Elliott, D.J. Sugars and cell adhesion: The role of ST6GalNAc1 in prostate cancer progression. Cancer Cell Microenviron. 2016, 3, e1174. [Google Scholar]
- Takenaka, Y.; Fukumori, T.; Raz, A. Galectin-3 and metastasis. Glycoconj. J. 2004, 19, 543–549. [Google Scholar] [CrossRef] [PubMed]
- Beatson, R.; Maurstad, G.; Picco, G.; Arulappu, A.; Coleman, J.; Wandell, H.H.; Clausen, H.; Mandel, U.; Taylor-Papadimitriou, J.; Sletmoen, M.; et al. The breast cancer-associated glycoforms of MUC1, MUC1-Tn and sialyl-Tn, are expressed in COSMC wild-type cells and bind the C-type lectin MGL. PLoS ONE 2015, 10, e0125994. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pinho, S.; Marcos, N.T.; Ferreira, B.; Carvalho, A.S.; Oliveira, M.J.; Santos-Silva, F.; Harduin-Lepers, A.; Reis, C.A. Biological significance of cancer-associated sialyl-Tn antigen: Modulation of malignant phenotype in gastric carcinoma cells. Cancer Lett. 2007, 249, 157–170. [Google Scholar] [CrossRef] [PubMed]
- Karsten, U.; Goletz, S. What makes cancer stem cell markers different? SpringerPlus 2013, 2. [Google Scholar] [CrossRef] [PubMed]
- Victorzon, M.; Nordling, S.; Nilsson, O.; Roberts, P.J.; Haglund, C. Sialyl Tn antigen is an independent predictor of outcome in patients with gastric cancer. Int. J. Cancer 1996, 65, 295–300. [Google Scholar] [CrossRef]
- Cao, Y.; Schlag, P.M.; Karsten, U. Immunodetection of epithelial mucin (MUC1, MUC3) and mucin-associated glycotopes (TF, Tn, and sialosyl-Tn) in benign and malignant lesions of colonic epithelium: Apolar localization corresponds to malignant transformation. Virchows Arch. 1997, 431, 159–166. [Google Scholar] [CrossRef] [PubMed]
- Carrilho, C.; Cantel, M.; Gouveia, P.; David, L. Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) and gp 230 mucin-like glycoprotein are candidate markers for neoplastic transformation of the human cervix. Virchows Arch. 2000, 437, 173–179. [Google Scholar] [CrossRef] [PubMed]
- Kinney, A.Y.; Sahin, A.; Vernon, S.W.; Frankowski, R.F.; Annegers, J.F.; Hortobagyi, G.N.; Buzdar, A.U.; Frye, D.K.; Dhingra, K. The prognostic significance of sialyl-Tn antigen in women treated with breast carcinoma treated with adjuvant chemotherapy. Cancer 1997, 80, 2240–2249. [Google Scholar] [CrossRef]
- Miles, D.W.; Happerfield, L.C.; Smith, P.; Gillibrand, R.; Bobrow, L.G.; Gregory, W.M.; Rubens, R.D. Expression of sialyl-Tn predicts the effect of adjuvant chemotherapy in node-positive breast cancer. Br. J. Cancer 1994, 70, 1272–1275. [Google Scholar] [CrossRef] [PubMed]
- Holmberg, L.A.; Sandmaier, B.M. Theratope vaccine (sTn-KLH). Expert Opin. Biol. Ther. 2001, 1, 881–891. [Google Scholar] [CrossRef] [PubMed]
- Morse, M.A. Technology evaluation: Theratope, biomira inc. Curr. Opin. Mol. Ther. 2000, 2, 453–458. [Google Scholar] [PubMed]
- Miles, D.; Roche, H.; Martin, M.; Perren, T.J.; Cameron, D.A.; Glaspy, J.; Dodwell, D.; Parker, J.; Mayordomo, J.; Tres, A.; et al. Phase III multicenter clinical trial of the sialyl-Tn (sTn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist 2011, 16, 1092–1100. [Google Scholar] [CrossRef] [PubMed]
- Ibrahim, N.K.; Murray, J.L. Clinical development of the sTn-KLH vaccine (Theratope®). Clin. Breast Cancer 2003, 3 (Suppl. 4), S139–S143. [Google Scholar] [CrossRef] [PubMed]
- Miles, D.; Papazisis, K. Rationale for the clinical development of sTn-KLH (Theratope®) and anti-MUC-1 vaccines in breast cancer. Clin. Breast Cancer 2003, 3 (Suppl. 4), S134–S138. [Google Scholar] [CrossRef] [PubMed]
- Blixt, O.; Bueti, D.; Burford, B.; Allen, D.; Julien, S.; Hollingsworth, M.; Gammerman, A.; Fentiman, I.; Taylor-Papadimitriou, J.; Burchell, J.M. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis. Breast Cancer Res. 2011, 13, R25. [Google Scholar] [CrossRef] [PubMed]
- Miles, D.W.; Towlson, K.E.; Graham, R.; Reddish, M.; Longenecker, B.M.; Taylor-Papadimitriou, J.; Rubens, R.D. A randomised phase II study of sialyl-Tn and DETOX-B adjuvant with or without cyclophosphamide pretreatment for the active specific immunotherapy of breast cancer. Br. J. Cancer 1996, 74, 1292–1296. [Google Scholar] [CrossRef] [PubMed]
- MacLean, G.D.; Reddish, M.A.; Koganty, R.R.; Longenecker, B.M. Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic sTn vaccine. J. Immunother. Emphas. Tumor Immunol. 1996, 19, 59–68. [Google Scholar] [CrossRef]
- Holmberg, L.A.; Sandmaier, B.M. Vaccination with Theratope® (sTn-KLH) as treatment for breast cancer. Expert Rev. Vaccines 2004, 3, 655–663. [Google Scholar] [CrossRef] [PubMed]
- MacLean, G.D.; Miles, D.W.; Rubens, R.D.; Reddish, M.A.; Longenecker, B.M. Enhancing the effect of Theratope® sTn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide. J. Immunother. Emphas. Tumor Immunol. 1996, 19, 309–316. [Google Scholar] [CrossRef]
- Reddish, M.A.; MacLean, G.D.; Poppema, S.; Berg, A.; Longenecker, B.M. Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope® sialyl-Tn-KLH cancer vaccine in active specific immunotherapy. Cancer Immunol. Immunother. 1996, 42, 303–309. [Google Scholar] [CrossRef] [PubMed]
- Mayordomo, J.; Tres, A.; Miles, D.; Finke, L.; Jenkins, H. Long-term follow-up of patients concomitantly treated with hormone therapy in a prospective controlled randomized multicenter clinical study comparing sTn-KLH vaccine with KLH control in stage IV breast cancer following first-line chemotherapy. J. Clin. Oncol. 2004, 22, 2603. [Google Scholar]
- Loureiro, L.R.; Carrascal, M.A.; Barbas, A.; Ramalho, J.S.; Novo, C.; Delannoy, P.; Videira, P.A. Challenges in antibody development against Tn and sialyl-Tn antigens. Biomolecules 2015, 5, 1783–1809. [Google Scholar] [CrossRef] [PubMed]
- Ponta, H.; Sherman, L.; Herrlich, P.A. CD44: From adhesion molecules to signalling regulators. Nat. Rev. Mol. Cell Biol. 2003, 4, 33–45. [Google Scholar] [CrossRef] [PubMed]
- Schjoldager, K.T.; Clausen, H. Site-specific protein O-glycosylation modulates proprotein processing—Deciphering specific functions of the large polypeptide galnac-transferase gene family. Biochim. Biophys. Acta 2012, 1820, 2079–2094. [Google Scholar] [CrossRef] [PubMed]
- Ohtsubo, K.; Marth, J.D. Glycosylation in cellular mechanisms of health and disease. Cell 2006, 126, 855–867. [Google Scholar] [CrossRef] [PubMed]
- Moremen, K.W.; Tiemeyer, M.; Nairn, A.V. Vertebrate protein glycosylation: Diversity, synthesis and function. Nat. Rev. Mol. Cell Biol. 2012, 13, 448–462. [Google Scholar] [CrossRef] [PubMed]
© 2016 by the author; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Munkley, J. The Role of Sialyl-Tn in Cancer. Int. J. Mol. Sci. 2016, 17, 275. https://doi.org/10.3390/ijms17030275
Munkley J. The Role of Sialyl-Tn in Cancer. International Journal of Molecular Sciences. 2016; 17(3):275. https://doi.org/10.3390/ijms17030275
Chicago/Turabian StyleMunkley, Jennifer. 2016. "The Role of Sialyl-Tn in Cancer" International Journal of Molecular Sciences 17, no. 3: 275. https://doi.org/10.3390/ijms17030275