Fucosyltransferase 6. GDP-Fucose Lactosamine α3-Fucosyltransferase (FUT6)

Reference work entry


Fuc-T VI was cloned as a fourth member of human α1→3/4 fucosyltransferase gene family by Weston et al. in 1992. The enzyme shared 85 % or 89 % amino acid sequence identity with previously cloned Fuc-T III or Fuc-T V, respectively, and the FUT6 gene encoding the enzyme was shown to be located on chromosome 19, where the genes for Fuc-T III or Fuc-T V are also located. Fuc-T VI is able to synthesize Lewis x and sialyl Lewis x, but not sialyl Lewis a or Lewis a. The enzyme turned out to be the “plasma-type” fucosyltransferase and is known to synthesize the sialyl Lewis x determinant carried by plasma proteins and epithelial cancer cells.


Epithelial Cancer Cell Fucose Residue Fourth Member Chain Substrate Fucosyltransferase Activity 


  1. Borsig L, Katopodis AG, Bowen BR, Berger EG (1998) Trafficking and localization studies of recombinant α1,3-fucosyltransferase VI stably expressed in CHO cells. Glycobiology 8:259–268PubMedCrossRefGoogle Scholar
  2. Borsig L, Imbach T, Höchli M, Berger EG (1999) α1,3Fucosyltransferase VI is expressed in HepG2 cells and codistributed with b1,4galactosyltransferase I in the Golgi apparatus and monensin-induced swollen vesicles. Glycobiology 9:1273–1280PubMedCrossRefGoogle Scholar
  3. Brinkman-Van der Linden ECM, Mollicone R, Oriol R, Larson G, van den Eijnden DH, Van Dijk W (1996) A missense mutation in the FUT6 gene results in total absence of α3-fucosylation of human a1-acid glycoprotein. J Biol Chem 271:14492–14495PubMedCrossRefGoogle Scholar
  4. Brinkman-Van der Linden EC, de Haan PF, Havenaar EC, Van Dijk W (1998) Inflammation-induced expression of sialyl LewisX is not restricted to α1-acid glycoprotein but also occurs to a lesser extent on a1-antichymotrypsin and haptoglobin. Glycoconj J 15:177–182PubMedCrossRefGoogle Scholar
  5. Britten CJ, Bird MI (1997) Chemical modification of an α3-fucosyltransferase; definition of amino acid residues essential for enzyme activity. Biochim Biophys Acta 1334:57–64PubMedCrossRefGoogle Scholar
  6. Cailleau-Thomas A, Coullin P, Candelier JJ, Balanzino L, Mennesson B, Oriol R, Mollicone R (2000) FUT4 and FUT9 genes are expressed early in human embryogenesis. Glycobiology 10:789–802PubMedCrossRefGoogle Scholar
  7. Cameron HS, Szczepaniak D, Weston BW (1995) Expression of human chromosome 19p α(1,3)-fucosyltransferase genes in normal tissues – alternative splicing, polyadenylation, and isoforms. J Biol Chem 270:20112–20122PubMedCrossRefGoogle Scholar
  8. Candelier JJ, Mollicone R, Mennesson B, Bergemer AM, Henry S, Coullin P, Oriol R (1993) α-3-fucosyltransferases and their glycoconjugate antigen products in the developing human kidney. Lab Invest 69:449–459PubMedGoogle Scholar
  9. Chandrasekaran EV, Rhodes JM, Jain RK, Matta KL (1994) Lactose as affinity eluent and a synthetic sulfated copolymer as inhibitor, in conjunction with synthetic and natural acceptors, differentiate human milk Lewis-type and plasma-type α-l-fucosyltransferases. Biochem Biophys Res Commun 198:350–358PubMedCrossRefGoogle Scholar
  10. Chen W, Tang J, Stanley P (2005) Suppressors of alpha(1,3)fucosylation identified by expression cloning in the LEC11B gain-of-function CHO mutant. Glycobiology 15:259–269PubMedCrossRefGoogle Scholar
  11. Chen G-Y, Osada H, Santamaria-Babi LF, Kannagi R (2006) Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes. Proc Natl Acad Sci USA 103:16894–16899PubMedCrossRefGoogle Scholar
  12. Costache M, Apoil PA, Cailleau A, Elmgren A, Larson G, Henry S, Blancher A, Iordachescu D, Oriol R, Mollicone R (1997a) Evolution of fucosyltransferase genes in vertebrates. J Biol Chem 272:29721–29728PubMedCrossRefGoogle Scholar
  13. Costache M, Cailleau A, Fernandez-Mateos P, Oriol R, Mollicone R (1997b) Advances in molecular genetics of α2- and α3/4-fucosyltransferases. Transfus Clin Biol 4:367–382PubMedCrossRefGoogle Scholar
  14. Dall’Olio F, Malagolini N, Trinchera M, Chiricolo M (2012) Mechanisms of cancer-associated glycosylation changes. Front Biosci 17:670–699CrossRefGoogle Scholar
  15. De Graaf TW, Van der Stelt ME, Anbergen MG, Van Dijk W (1993) Inflammation-induced expression of sialyl Lewis X-containing glycan structures on alpha 1-acid glycoprotein (orosomucoid) in human sera. J Exp Med 177:657–666PubMedCrossRefGoogle Scholar
  16. De Vries T, Palcic MP, Schoenmakers PS, van den Eijnden DH, Joziasse DH (1997) Acceptor specificity of GDP-Fuc:Galβ1-->4GlcNAc-R α3-fucosyltransferase VI (FucT VI) expressed in insect cells as soluble, secreted enzyme. Glycobiology 7:921–927PubMedCrossRefGoogle Scholar
  17. Dohi T, Hashiguchi M, Yamamoto S, Morita H, Oshima M (1994) Fucosyltransferase-producing sialyl Lea and sialyl Lex carbohydrate antigen in benign and malignant gastrointestinal mucosa. Cancer 73:1552–1561PubMedCrossRefGoogle Scholar
  18. Guo Q, Guo B, Wang Y, Wu J, Jiang W, Zhao S, Qiao S, Wu Y (2012) Functional analysis of α1,3/4-fucosyltransferase VI in human hepatocellular carcinoma cells. Biochem Biophys Res Commun 417:311–317PubMedCrossRefGoogle Scholar
  19. Hada T, Fukui K, Ohno M, Akamatsu S, Yazawa S, Enomoto K, Yamaguchi K, Matsuda Y, Amuro Y, Yamanaka N (1995) Increased plasma α(1->3)-l-fucosyltransferase activities in patients with hepatocellular carcinoma. Glycoconj J 12:627–631PubMedCrossRefGoogle Scholar
  20. Havenaar EC, Hoff RC, van den Eijnden DH, Van Dijk W (1998) Sialyl Lewisx epitopes do not occur on acute phase proteins in mice: relationship to the absence of a3-fucosyltransferase in the liver. Glycoconj J 15:389–395PubMedCrossRefGoogle Scholar
  21. Higai K, Miyazaki N, Azuma Y, Matsumoto K (2006) Interleukin-1beta induces sialyl Lewis X on hepatocellular carcinoma HuH-7 cells via enhanced expression of ST3Gal IV and FUT VI gene. FEBS Lett 580:6069–6075PubMedCrossRefGoogle Scholar
  22. Higai K, Miyazaki N, Azuma Y, Matsumoto K (2008) Transcriptional regulation of the fucosyltransferase VI gene in hepatocellular carcinoma cells. Glycoconj J 25:225–235PubMedCrossRefGoogle Scholar
  23. Hiller KM, Mayben JP, Bendt KM, Manousos GA, Senger K, Cameron HS, Weston BW (2000) Transfection of a(1,3)fucosyltransferase antisense sequences impairs the proliferative and tumorigenic ability of human colon carcinoma cells. Mol Carcinog 27:280–288PubMedCrossRefGoogle Scholar
  24. Huffman JE, Knezevic A, Vitart V, Kattla J, Adamczyk B, Novokmet M, Igl W, Pucic M, Zgaga L, Johannson A, Redzic I, Gornik O, Zemunik T, Polasek O, Kolcic I, Pehlic M, Koeleman CA, Campbell S, Wild SH, Hastie ND, Campbell H, Gyllensten U, Wuhrer M, Wilson JF, Hayward C, Rudan I, Rudd PM, Wright AF, Lauc G (2011) Polymorphisms in B3GAT1, SLC9A9 and MGAT5 are associated with variation within the human plasma N-glycome of 3533 European adults. Hum Mol Genet 20:5000–5011PubMedCrossRefGoogle Scholar
  25. Hutchinson WL, Du MQ, Johnson PJ, Williams R (1991) Fucosyltransferases: differential plasma and tissue alterations in hepatocellular carcinoma and cirrhosis. Hepatology 13:683–688PubMedCrossRefGoogle Scholar
  26. Ikeda N, Eguchi H, Nishihara S, Narimatsu H, Kannagi R, Irimura T, Ohta M, Matsuda H, Taniguchi N, Honke K (2001) A remodeling system of the 3′-sulfo Lewis a and 3′-sulfo Lewis x epitopes. J Biol Chem 276:38588–38594PubMedCrossRefGoogle Scholar
  27. Ito H, Hiraiwa N, Sawada-Kasugai M, Akamatsu S, Tachikawa T, Kasai Y, Akiyama S, Ito K, Takagi H, Kannagi R (1997) Altered mRNA expression of specific molecular species of fucosyl- and sialyltransferases in human colorectal cancer tissues. Int J Cancer 71:556–564PubMedCrossRefGoogle Scholar
  28. Izawa M, Kumamoto K, Mitsuoka C, Kanamori A, Ohmori K, Ishida H, Nakamura S, Kurata-Miura K, Sasaki K, Nishi T, Kannagi R (2000) Expression of sialyl 6-sulfo Lewis x is inversely correlated with conventional sialyl Lewis x expression in human colorectal cancer. Cancer Res 60:1410–1416PubMedGoogle Scholar
  29. Johnson PH, Donald AS, Clarke JL, Watkins WM (1995) Purification, properties and possible gene assignment of an α1,3-fucosyltransferase expressed in human liver. Glycoconj J 12:879–893PubMedCrossRefGoogle Scholar
  30. Kannagi R (1997) Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer. Glycoconj J 14:577–584PubMedCrossRefGoogle Scholar
  31. Kannagi R, Izawa M, Koike T, Miyazaki K, Kimura N (2004) Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci 95:377–384PubMedCrossRefGoogle Scholar
  32. Kannagi R, Miyazaki K, Kimura N, Yin J (2007) Selectin-mediated metastasis of tumor cells: alteration of carbohydrate-mediated cell-cell interactions in cancers induced by epigenetic silencing of glycogenes. In: Sansom C, Markman O (eds) Glycobiology. Scion, Bloxham, pp 274–287Google Scholar
  33. Kaplan JC, Kahn A, Chelly J (1992) Illegitimate transcription: its use in the study of inherited disease. Hum Mutat 1:357–360PubMedCrossRefGoogle Scholar
  34. Karaivanova V, Mookerjea S, Hunt D, Nagpurkar A (1996) Characterization and purification of fucosyltransferases from the cytosol of rat colon. Int J Biochem Cell Biol 28:165–174PubMedCrossRefGoogle Scholar
  35. Koda Y, Soejima M, Kimura H (2001) The polymorphisms of fucosyltransferases. Leg Med (Tokyo) 3:2–14CrossRefGoogle Scholar
  36. Koszdin KL, Bowen BR (1992) The cloning and expression of a human α-1,3 fucosyltransferase capable of forming the E-selection ligand. Biochem Biophys Res Commun 187:152–157PubMedCrossRefGoogle Scholar
  37. Larson G, Borjeson C, Elmgren A, Kernholt A, Henry S, Fletcher A, Aziz A, Mollicone R, Oriol R (1996) Identification of a new plasma α(1,3)fucosyltransferase (FUT6) allele requires an extended genotyping strategy. Vox Sang 71:233–241PubMedCrossRefGoogle Scholar
  38. Lauc G, Zoldos V (2011) The role of epigenetic regulation of membrane glycoconjugates in the attenuation of viral pandemics. Med Hypotheses 76:214–216PubMedCrossRefGoogle Scholar
  39. Lauc G, Essafi A, Huffman JE, Hayward C, Knezevic A, Kattla JJ, Polasek O, Gornik O, Vitart V, Abrahams JL, Pucic M, Novokmet M, Redzic I, Campbell S, Wild SH, Borovecki F, Wang W, Kolcic I, Zgaga L, Gyllensten U, Wilson JF, Wright AF, Hastie ND, Campbell H, Rudd PM, Rudan I (2010) Genomics meets glycomics-the first GWAS study of human N-Glycome identifies HNF1aas a master regulator of plasma protein fucosylation. PLoS Genet 6:e1001256PubMedCentralPubMedCrossRefGoogle Scholar
  40. Leppänen A, Mehta P, Ouyang YB, Ju T, Helin J, Moore KL, van Die I, Canfield WM, McEver RP, Cummings RD (1999) A novel glycosulfopeptide binds to P-selectin and inhibits leukocyte adhesion to P-selectin. J Biol Chem 274:24838–24848PubMedCrossRefGoogle Scholar
  41. Lin X, Lu D, Gao Y, Tao S, Yang X, Feng J, Tan A, Zhang H, Hu Y, Qin X, Kim ST, Peng T, Li L, Mo L, Zhang S, Trent JM, Mo Z, Zheng SL, Xu J, Sun J (2012) Genome-wide association study identifies novel loci associated with serum level of vitamin B12 in Chinese men. Hum Mol Genet 21:2610–2617PubMedCrossRefGoogle Scholar
  42. Liu YC, Yen HY, Chen CY, Chen CH, Cheng PF, Juan YH, Khoo KH, Yu CJ, Yang PC, Hsu TL, Wong CH (2011) Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc Natl Acad Sci USA 108:11332–11337PubMedCrossRefGoogle Scholar
  43. Lowe JB (1997) Selectin ligands, leukocyte trafficking, and fucosyltransferase genes. Kidney Int 51:1418–1426PubMedCrossRefGoogle Scholar
  44. Lu L, Hou X, Shi S, Korner C, Stanley P (2010) Slc35c2 promotes Notch1 Fucosylation and is required for optimal Notch signaling in mammalian cells. J Biol Chem 285:36245–36254PubMedCrossRefGoogle Scholar
  45. Malissard M, Zeng S, Berger EG (2000) Expression of functional soluble forms of human b-1, 4-galactosyltransferase I, α-2,6-sialyltransferase, and α-1, 3-fucosyltransferase VI in the methylotrophic yeast, Pichia pastoris. Biochem Biophys Res Commun 267:169–173PubMedCrossRefGoogle Scholar
  46. Mas E, Pasqualini E, Caillol N, El Battari A, Crotte C, Lombardo D, Sadoulet MO (1998) Fucosyltransferase activities in human pancreatic tissue: comparative study between cancer tissues and established tumoral cell lines. Glycobiology 8:605–613PubMedCrossRefGoogle Scholar
  47. Matsuura N, Narita T, Hiraiwa N, Hiraiwa M, Murai H, Iwase T, Funahashi H, Imai T, Takagi H, Kannagi R (1998) Gene expression of fucosyl- and sialyl-transferases which synthesize sialyl Lewisx, the carbohydrate ligands for E-selectin, in human breast cancer. Int J Oncol 12:1157–1164PubMedGoogle Scholar
  48. McCurley RS, Recinos A, Olsen AS, Gingrich JC, Szczepaniak D, Cameron HS, Krauss R, Weston BW (1995) Physical maps of human α(1,3)fucosyltransferase genes FUT3–FUT6 on chromosomes 19p13.3 and 11q21. Genomics 26:142–146PubMedCrossRefGoogle Scholar
  49. Mitsuoka C, Sawada-Kasugai M, Ando-Furui K, Izawa M, Nakanishi H, Nakamura S, Ishida H, Kiso M, Kannagi R (1998) Identification of a major carbohydrate capping group of the L-selectin ligand on high endothelial venules in human lymph nodes as 6-sulfo sialyl Lewis x. J Biol Chem 273:11225–11233PubMedCrossRefGoogle Scholar
  50. Mollicone R, Gibaud A, Francois A, Ratcliffe M, Oriol R (1990) Acceptor specificity and tissue distribution of three human α-3-fucosyltransferases. Eur J Biochem 191:169–176PubMedCrossRefGoogle Scholar
  51. Mollicone R, Reguigne I, Fletcher A, Aziz A, Rustam M, Weston BW, Kelly RJ, Lowe JB, Oriol R (1994) Molecular basis for plasma α(1,3)-fucosyltransferase gene deficiency (FUT6). J Biol Chem 269:12662–12671PubMedGoogle Scholar
  52. Natsuka S, Gersten KM, Zenita K, Kannagi R, Lowe JB (1994) Molecular cloning of a cDNA encoding a novel human leukocyte α-1, 3-fucosyltransferase capable of synthesizing the sialyl Lewis x determinant. J Biol Chem 269:16789–16794PubMedGoogle Scholar
  53. Nimtz M, Grabenhorst E, Gambert U, Costa J, Wray V, Morr M, Thiem J, Conradt HS (1998) In vitro a1-3 or a1-4 fucosylation of type I and II oligosaccharides with secreted forms of recombinant human fucosyltransferases III and VI. Glycoconj J 15:873–883PubMedCrossRefGoogle Scholar
  54. Nishihara S, Nakazato M, Kudo T, Kimura H, Ando T, Narimatsu H (1993) Human a-1,3 fucosyltransferase (FucT-VI) gene is located at only 13 kb 3′ to the Lewis type fucosyltransferase (FucT-III) gene on chromosome 19. Biochem Biophys Res Commun 190:42–46PubMedCrossRefGoogle Scholar
  55. Oriol R, Mollicone R, Cailleau A, Balanzino L, Breton C (1999) Divergent evolution of fucosyltransferase genes from vertebrates, invertebrates, and bacteria. Glycobiology 9:323–334PubMedCrossRefGoogle Scholar
  56. Oulmouden A, Wierinckx A, Petit JM, Costache M, Palcic MM, Mollicone R, Oriol R, Julien R (1997) Molecular cloning and expression of a bovine α(1,3)-fucosyltransferase gene homologous to a putative ancestor gene of the human FUT3-FUT5-FUT6 cluster. J Biol Chem 272:8764–8773PubMedCrossRefGoogle Scholar
  57. Pang H, Koda Y, Soejima M, Schlaphoff T, Du Toit ED, Kimura H (1999) Allelic diversity of the human plasma α(1,3)fucosyltransferase gene (FUT6). Ann Hum Genet 63:277–284PubMedCrossRefGoogle Scholar
  58. Petretti T, Schulze B, Schlag PM, Kemmner W (1999) Altered mRNA expression of glycosyltransferases in human gastric carcinomas. Biochim Biophys Acta 1428:209–218PubMedCrossRefGoogle Scholar
  59. Petretti T, Kemmner W, Schulze B, Schlag PM (2000) Altered mRNA expression of glycosyltransferases in human colorectal carcinomas and liver metastases. Gut 46:359–366PubMedCrossRefGoogle Scholar
  60. Raychoudhury SS, Millette CF (1995) Glycosidic specificity of fucosyltransferases present in rat epididymal spermatozoa. J Androl 16:448–456PubMedGoogle Scholar
  61. Sasaki K, Kurata K, Funayama K, Nagata M, Watanabe E, Ohta S, Hanai N, Nishi T (1994) Expression cloning of a novel α1,3-fucosyltransferase that is involved in biosynthesis of the sialyl Lewis x carbohydrate determinants in leukocytes. J Biol Chem 269:14730–14737PubMedGoogle Scholar
  62. Schnyder-Candrian S, Borsig L, Moser R, Berger EG (2000) Localization of ò1,3-fucosyltransferase VI in Weibel-Palade bodies of human endothelial cells. Proc Natl Acad Sci USA 97:8369–8374PubMedCrossRefGoogle Scholar
  63. Sherwood AL, Holmes EH (1999) Analysis of the expression and enzymatic properties of α1->3 fucosyltransferase from human lung carcinoma NCI-H69 and PC9 cells. Glycobiology 9:637–643PubMedCrossRefGoogle Scholar
  64. Stern HM, Padilla M, Wagner K, Amler L, Ashkenazi A (2010) Development of immunohistochemistry assays to assess GALNT14 and FUT3/6 in clinical trials of dulanermin and drozitumab. Clin Cancer Res 16:1587–1596PubMedCrossRefGoogle Scholar
  65. Takada A, Ohmori K, Takahashi N, Tsuyuoka K, Yago K, Zenita K, Hasegawa A, Kannagi R (1991) Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A. Biochem Biophys Res Commun 179:713–719PubMedCrossRefGoogle Scholar
  66. Takada A, Ohmori K, Yoneda T, Tsuyuoka K, Hasegawa A, Kiso M, Kannagi R (1993) Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium. Cancer Res 53:354–361PubMedGoogle Scholar
  67. Thompson S, Matta KL, Turner GA (1991) Changes in fucose metabolism associated with heavy drinking and smoking: a preliminary report. Clin Chim Acta 201:59–64PubMedCrossRefGoogle Scholar
  68. Trinchera M, Malagolini N, Chiricolo M, Santini D, Minni F, Caretti A, Dall’Olio F (2011) The biosynthesis of the selectin-ligand sialyl Lewis x in colorectal cancer tissues is regulated by fucosyltransferase VI and can be inhibited by an RNA interference-based approach. Int J Biochem Cell Biol 43:130–139PubMedCrossRefGoogle Scholar
  69. Wagner KW, Punnoose EA, Januario T, Lawrence DA, Pitti RM, Lancaster K, Lee D, von Goetz M, Yee SF, Totpal K, Huw L, Katta V, Cavet G, Hymowitz SG, Amler L, Ashkenazi A (2007) Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 13:1070–1077PubMedCrossRefGoogle Scholar
  70. Weston BW, Smith PL, Kelly RJ, Lowe JB (1992) Molecular cloning of a fourth member of a human A(1, 3)fucosyltransferase gene family. Multiple homologous sequences that determine expression of the Lewis x, sialyl Lewis x, and difucosyl sialyl Lewis x epitopes. J Biol Chem 267:24575–24584PubMedGoogle Scholar
  71. Weston BW, Hiller KM, Mayben JP, Manousos GA, Bendt KM, Liu R, Cusack JC Jr (1999) Expression of human a(1,3)fucosyltransferase antisense sequences inhibits selectin-mediated adhesion and liver metastasis of colon carcinoma cells. Cancer Res 59:2127–2135PubMedGoogle Scholar
  72. Yago K, Zenita K, Ginya H, Sawada M, Ohmori K, Okuma M, Kannagi R, Lowe JB (1993) Expression of α(1,3)fucosyltransferases which synthesize sialyl Lex and sialyl Lea, the carbohydrate ligands for E- and P-selectins, in human malignant cell lines. Cancer Res 53:5559–5565PubMedGoogle Scholar
  73. Yazawa S, Tanaka S, Nishimura T, Miyanaga K, Kochibe N (1999) Plasma a1,3-fucosyltransferase deficiency in schizophrenia. Exp Clin Immunogenet 16:125–130PubMedCrossRefGoogle Scholar
  74. Zhang A, Potvin B, Zaiman A, Chen W, Kumar R, Phillips L, Stanley P (1999) The gain-of-function Chinese hamster ovary mutant LEC11B expresses one of two Chinese hamster FUT6 genes due to the loss of a negative regulatory factor. J Biol Chem 274:10439–10450PubMedCrossRefGoogle Scholar
  75. Zoldos V, Horvat T, Novokmet M, Cuenin C, Muzinic A, Pucic M, Huffman JE, Gornik O, Polasek O, Campbell H, Hayward C, Wright AF, Rudan I, Owen K, McCarthy MI, Herceg Z, Lauc G (2012) Epigenetic silencing of HNF1A associates with changes in the composition of the human plasma N-glycome. Epigenetics 7:164–172PubMedCrossRefGoogle Scholar
  76. Zoldos V, Novokmet M, Beceheli I, Lauc G (2013) Genomics and epigenomics of the human glycome. Glycoconj J 30:41–50Google Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Advanced Medical Research CenterAichi Medical UniversityNagakuteJapan

Personalised recommendations