Year 2015 / Volume 107 / Number 10
Original
Screening of enzymatic synthesis and expression of Lewis determinants in human colorectal carcinoma

598-607

DOI: 10.17235/reed.2015.3789/2015

Almudena Fernández-Briera, Elisa Cuevas, Emilio Gil-Martín,

Abstract
Background: Although colorectal carcinogenesis has been intensively studied, the published investigations do not provide a consistent description of how different carbohydrate determinants of colorectal epithelium are modified in colorectal cancer (CRC). Objective: This study is an attempt to characterize the terminal fucosylation steps responsible for the synthesis of mono- Le(a)/Le(x)- and difucosylated -Le(b)/Le(y)- Lewis antigens in healthy and tumour CRC tissue. Methods: An immunohistochemical study of Lewis antigens’ expression was undertaken, along with screening of the fucosyltransferase (FT) activities involved in their synthesis, on healthy and tumour samples from 18 patients undergoing CRC. Results: Analysis of alpha(1,2/3/4)FT activities involved in the sequential fucosylation of cores 1 and 2 showed significant increases in tumour tissue. Expressed as microU/mg and control vs. tumour activity (pfrom Wilcoxon’s test), the FT activities for Le(a)/Le(b) synthesis were: lacto-N-biose alpha(1,2)/alpha(1,4)FT, 65.4 ± 19.0 vs. 186 ± 35.1 (p< 0.005); lacto-N-fucopentaose 1 alpha(1,4)FT, 64.9 ± 11.9 vs. 125.4 ± 20.7 (p< 0.005); Le(a) alpha(1,2)FT, 56.2 ± 7.2 vs. 130.5 ± 15.6 (p< 0.001). Similarly, for Le(x)/Le(y) synthesis were: N-acetyllactosamine alpha(1,2)-/alpha(1,3)FT, 53.4 ± 12.2 vs. 108.1 ± 18.9 (p< 0.001); 2’-Fucosyl-N-acetyllactosamine alpha(1,3)FT, 61.3 ± 10.7 vs. 126.4 ± 22.9 (p< 0.001); 2’-Fucosyllactose alpha(1,3)FT, 38.9 ± 10.9 vs. 143.6 ± 28.9 (p< 0.001); 2’-Methyllactose alpha(1,3)FT, 30.9 ± 4.8 vs. 66.1 ± 8.1 (p< 0.005); and Le(x) alpha(1,2)FT, 54.3 ± 11.9 vs. 88.2 ± 14.4 (p< 0.001). Immunohistochemical Le(y) expression was increased (p< 0.01 according to Wilcoxon’s test) in tumour tissue, with 84.6% of specimens being positive: 7.7% weak, 15.4% moderate and 61.5% high intensity. Conclusions: Results suggest the activation of the biosynthesis pathways of mono- and difucosylated Lewis histo-blood antigens in tumour tissue from CRC patients, leading to the overexpression of Le(y), probably at the expense of Le(x).
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References
1. Chen CC, Yang SH, Lin JK, et al. Is it reasonable to add preoperative serum level of CEA and CA 19-9 to staging for colorectal cancer? J Surg Res 2005; 124: 169-74.
2. Apweiler R, Hermjakob H, Sharon N. On the frequency of protein glycosylation, as deduced from analysis of the SWISS.PROT database. Biochim Biophys Acta 1999; 1473: 4-8.
3. Coutinho PM, Deleury E, Davies GJ, et al. An evolving hierarchical family classification for glycosyltransferases. J Mol Biol 2003; 328: 307-17.
4. Hakomori S. Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res 1996 56: 5309-18.
5. Staudacher E, Altmann F, Wilson IBH, et al. Fucose in N-glycans: from plant to man. Biochim Biophys Acta 1999; 1473: 216-36.
6. Miyoshi E, Moriwaki K, Nakagawa T. Biological function of fucosylation in cancer biology. J Biochem 2008; 143: 725-29.
7. Miyoshi E, Moriwaki K, Terao N, et al. Fucosylation is a promising target for cancer diagnosis and therapy. Biomolecules 2012; 2: 34-45.
8. Moriwaki K, Miyoshi E. Fucosylation and gastrointestinal cancer. World J Hepatol 2010; 2: 151-61.
9. Listinsky JJ, Siegal JP, Listinsky CM. The emerging importance of -L-fucose in human breast cancer: a review. Am J Transl Res 2011; 3: 292-322.
10. Becker DJ, Lowe JB. Fucose: biosynthesis and biological function in mammals. Glycobiology 2003; 13: 41R-53R.
11. Le Pendu J, Marionneau S, Cailleau-Thomas A, et al. ABH and Lewis histo-blood group antigens in cancer. APMIS 2001; 109: 9-31.
12. Kokowska-Latallo JF, Larsen RD, Nair RP, et al. A cloned human cDNA determines expression of a mouse stage-specific embryonic antigen and the Lewis blood group alpha(1,3/1,4)fucosyltransferase. Genes Dev 1990; 4 : 1288-303.
13. Muinelo-Romay L, Gil-Martín E, Fernández-Briera A. (1,2)fucosylation in human colorectal carcinoma. Oncol Lett 2010; 1: 361-6.
14. Kim YS, Yuan M, Itzkowitz SH, et al. Expression of Ley and extended Ley blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues. Cancer Res 1986; 46: 5985-92.
15. Wolf BC, Salem RR, Sears HF, et al. The expression of colorectal carcinoma-associated antigens in the normal colonic mucosa. An immunohistochemical analysis of regional distribution. Am J Pathol 1989; 135: 111-9.
16. Schoentag R, Primus FJ, Kuhns W. ABH and Lewis blood group expression in colorectal carcinoma. Cancer Res 1987; 47: 1695-700.
17. Holmes EH, Ostrander GK, Clausen H, et al. Oncofetal expression of Lex carbohydrate antigens in human colonic adenocarcinomas. J Biol Chem 1987; 262: 11331-8.
18. Kim YS, Itzkowitz SH. Carbohydrate antigen expression in adenoma-carcinoma sequence. Prog Clin Biol Res 1988; 279: 241-50.
19. Naitoh H, Nakajima T, Nagamachi Y, et al. A clinicopathological evaluation of anti fucosylated antigen antibody (YB-2) in colorectal carcinoma. Glycosylation Dis 1994; 1: 31-6.
20. Nakagoe T, Fukushima K, Hirota M, et al. An immunohistochemical employer of monoclonal antibodies against Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens in primary colorectal, carcinomas and lymph node and hepatic lesions. J Gastroenterol 1994; 29: 129-38.
21. Blaszczyk M, Pak KY, Herlyn M, et al. Characterization of Lewis antigens in normal colon and gastrointestinal adenocarcinomas. Proc Natl Acad Sci 1985; 82: 3552-6.
22. Muramatsu T. Carbohydrate signals in metastasis and prognosis of human carcinomas. Glycobiology 1993; 3: 294-96.
23. Park SY, Lee SH, Kawasaki N, et al. 1-3/4 fucosylation at Asn 241 of -haptoglobin is a novel marker for colon cancer: a combinatorial approach for development of glycan biomarkers. Int J Cancer 2011; 130: 2366-76.
24. Dukes CE. The classification of cancer of the rectum. J Pathol Bacteriol 1932; 35: 323-32.
25. Sobin H, Wittekind CH. TNM classification of malignant tumours, 6th ed. Wiley-Liss. New York; 2002. pp 72-76.
26. Ernst CS, Shen JW, Litwin S, et al. Multiparameter evaluation of the expression in situ of normal and tumor-associated antigens in human colorectal carcinoma. J Natl Cancer Inst 1986; 77: 387-95.
27. Sakamoto J, Furukawa K, Gordon-Cardo C, et al. Expression of Lewisa, Lewisb, X and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines. Cancer Res 1986; 46: 1553-61.
28. Blasco E, Torrado J, Cosme A, et al. Expression of Lewis antigenic determinants in colorectal adenocarcinomas. J Exp Cell Biol 1989; 57: 153-8.
29. Ørntoft T, Holmes EH, Johnson P, et al. Differential tissue expression of the Lewis blood group antigens: enzymatic, immunohistologic, and immunohistochemical evidence for Lewis a and b antigen expression in Le(a-b-) individuals. Blood 1991; 77: 1389-96.
30. Goupille C, Marionneau S, Bureau V, et al. α(1,2)fucosyltransferase increases resistance to apoptosis of rat colon carcinoma cells. Glycobiology 2000; 10: 375-82.
31. Chandrasekaran EV, Jain RK, Rhodes JM, et al. Expression of blood group Lewis b determinant from Lewis a: association of this novel α(1,2)-L-fucosylating activity with the Lewis type α(1,3/4)-L-fucosyltransferase. Biochemistry 1995; 34: 4748-56.
32. Nakamura JI, Mogi A, Asao T, et al. Evidence that the aberrant (1,2)fucosyltransferase found in colorectal carcinoma may be encoded by FUT III (Le gene). Anticancer Res 1997; 17: 4563-69.
33. Yazawa S, Nakamura J, Asao T, et al. Aberrant α1→2fucosyltransferase found in human colorectal carcinoma involved in the accumulation of Leb and Y antigens in colorectal tumors. Jpn J Cancer Res 1993; 84: 989-95.
34. Yazawa S, Nishimura T, Ide M, et al. Tumor-related expression of 1,2fucosylated antigens on colorectal carcinoma cells and its suppression by cell-mediated priming using sugar acceptors for 1,2fucosyltransferase. Glycobiology 2002; 12: 545-53.
35. Ruan S, Lloyd KO. Glycosylation pathways in the biosynthesis of gangliosides in melanoma and neuroblastoma cells: relative glycosyltransferases levels determine ganglioside patterns. Cancer Res 1992; 70: 1467-76.
36. Villar-Portela S, Vázquez-Martín C, Muinelo-Romay L, et al. sLea and sLex expression in colorectal cancer: implications for tumourigenesis and disease prognosis. Histol Histopathol 2011; 26: 1305-16.
37. Kannagi R, Izawa M, Koike T, et al. Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci 2004; 95: 377-84.
38. Sun J, Thurin J, Cooper HS, et al. Elevated expression of H-type GDP-L-fucose:β-D-galactoside α-2-L-fucosyltransferase is associated with human colon-adenocarcinoma progression. Proc Natl Acad Sci 1995; 92: 5724-8.
39. Yazawa S, Madiyalakan R, Izawa H, et al. Cancer-associated elevation of (1,3)activity in human serum. Cancer 1988; 62: 516-20.
40. Nakagoe T, Fukushima K, Hirota M, et al. An immunohistochemical study of the distribution of blood group substances and related antigens in primary colorectal carcinomas and metastatic lymph node and liver lesions, using antibodies against A, B, H type 2, Le(a), and Le(x) antigens. J Gastroenterol 1994; 29: 265-75.
41. Cordon-Cardo C, Lloyd K.O, Sakamoto J, et al. Immunohistologic expression of blood-group antigens in normal human gastrointestinal tract and colonic carcinoma. Int J Cancer 1986; 37: 667-76.
42. Bara J, Mollicone R, Herreo-Zabaleta E, et al. Ectopic expression of the Y (Ley) antigen defined by monoclonal antibody 12-4LE in distal colonic adenocarcinomas. Int J Cancer 1988; 41: 683-9.
43. Hakomori S, Nudelman E, Levery SB, et al. Novel fucolipids accumulating in human adenocarcinoma. I. Glicolipids with di- or tri- fucosylated type 2 chain. J Biol Chem 1984; 259: 4672-80.
44. Cooper HS, Malecha MJ, Bass C, et al. Expression of blood group antigens H-2, Ley, and sialylated-Lea in human colorectal carcinoma. Am J Pathol 1991; 138: 103-10.
45. Prokopishyn NL, Puzon-McLaughlin W, Takada Y, et al. Integrin alpha3beta1 expressed by human colon cancer cells is a major carrier of oncodevelopmental carbohydrate epitopes. J Cell Biochem 1999; 72: 189-209.
46. Trail PA, Willner D, Bianchi AB, et al. Enhanced antitumor activity of paclitaxel in combination with the anticarcinoma immunoconjugate BR96-doxorubicin. Clin Cancer Res 1999; 5: 3632-8.
1. Chen CC, Yang SH, Lin JK, et al. Is it reasonable to add preoperative serum level of CEA and CA 19-9 to staging for colorectal cancer? J Surg Res 2005; 124: 169-74.
2. Apweiler R, Hermjakob H, Sharon N. On the frequency of protein glycosylation, as deduced from analysis of the SWISS.PROT database. Biochim Biophys Acta 1999; 1473: 4-8.
3. Coutinho PM, Deleury E, Davies GJ, et al. An evolving hierarchical family classification for glycosyltransferases. J Mol Biol 2003; 328: 307-17.
4. Hakomori S. Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res 1996 56: 5309-18.
5. Staudacher E, Altmann F, Wilson IBH, et al. Fucose in N-glycans: from plant to man. Biochim Biophys Acta 1999; 1473: 216-36.
6. Miyoshi E, Moriwaki K, Nakagawa T. Biological function of fucosylation in cancer biology. J Biochem 2008; 143: 725-29.
7. Miyoshi E, Moriwaki K, Terao N, et al. Fucosylation is a promising target for cancer diagnosis and therapy. Biomolecules 2012; 2: 34-45.
8. Moriwaki K, Miyoshi E. Fucosylation and gastrointestinal cancer. World J Hepatol 2010; 2: 151-61.
9. Listinsky JJ, Siegal JP, Listinsky CM. The emerging importance of -L-fucose in human breast cancer: a review. Am J Transl Res 2011; 3: 292-322.
10. Becker DJ, Lowe JB. Fucose: biosynthesis and biological function in mammals. Glycobiology 2003; 13: 41R-53R.
11. Le Pendu J, Marionneau S, Cailleau-Thomas A, et al. ABH and Lewis histo-blood group antigens in cancer. APMIS 2001; 109: 9-31.
12. Kokowska-Latallo JF, Larsen RD, Nair RP, et al. A cloned human cDNA determines expression of a mouse stage-specific embryonic antigen and the Lewis blood group alpha(1,3/1,4)fucosyltransferase. Genes Dev 1990; 4 : 1288-303.
13. Muinelo-Romay L, Gil-Martín E, Fernández-Briera A. (1,2)fucosylation in human colorectal carcinoma. Oncol Lett 2010; 1: 361-6.
14. Kim YS, Yuan M, Itzkowitz SH, et al. Expression of Ley and extended Ley blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues. Cancer Res 1986; 46: 5985-92.
15. Wolf BC, Salem RR, Sears HF, et al. The expression of colorectal carcinoma-associated antigens in the normal colonic mucosa. An immunohistochemical analysis of regional distribution. Am J Pathol 1989; 135: 111-9.
16. Schoentag R, Primus FJ, Kuhns W. ABH and Lewis blood group expression in colorectal carcinoma. Cancer Res 1987; 47: 1695-700.
17. Holmes EH, Ostrander GK, Clausen H, et al. Oncofetal expression of Lex carbohydrate antigens in human colonic adenocarcinomas. J Biol Chem 1987; 262: 11331-8.
18. Kim YS, Itzkowitz SH. Carbohydrate antigen expression in adenoma-carcinoma sequence. Prog Clin Biol Res 1988; 279: 241-50.
19. Naitoh H, Nakajima T, Nagamachi Y, et al. A clinicopathological evaluation of anti fucosylated antigen antibody (YB-2) in colorectal carcinoma. Glycosylation Dis 1994; 1: 31-6.
20. Nakagoe T, Fukushima K, Hirota M, et al. An immunohistochemical employer of monoclonal antibodies against Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens in primary colorectal, carcinomas and lymph node and hepatic lesions. J Gastroenterol 1994; 29: 129-38.
21. Blaszczyk M, Pak KY, Herlyn M, et al. Characterization of Lewis antigens in normal colon and gastrointestinal adenocarcinomas. Proc Natl Acad Sci 1985; 82: 3552-6.
22. Muramatsu T. Carbohydrate signals in metastasis and prognosis of human carcinomas. Glycobiology 1993; 3: 294-96.
23. Park SY, Lee SH, Kawasaki N, et al. 1-3/4 fucosylation at Asn 241 of -haptoglobin is a novel marker for colon cancer: a combinatorial approach for development of glycan biomarkers. Int J Cancer 2011; 130: 2366-76.
24. Dukes CE. The classification of cancer of the rectum. J Pathol Bacteriol 1932; 35: 323-32.
25. Sobin H, Wittekind CH. TNM classification of malignant tumours, 6th ed. Wiley-Liss. New York; 2002. pp 72-76.
26. Ernst CS, Shen JW, Litwin S, et al. Multiparameter evaluation of the expression in situ of normal and tumor-associated antigens in human colorectal carcinoma. J Natl Cancer Inst 1986; 77: 387-95.
27. Sakamoto J, Furukawa K, Gordon-Cardo C, et al. Expression of Lewisa, Lewisb, X and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines. Cancer Res 1986; 46: 1553-61.
28. Blasco E, Torrado J, Cosme A, et al. Expression of Lewis antigenic determinants in colorectal adenocarcinomas. J Exp Cell Biol 1989; 57: 153-8.
29. Ørntoft T, Holmes EH, Johnson P, et al. Differential tissue expression of the Lewis blood group antigens: enzymatic, immunohistologic, and immunohistochemical evidence for Lewis a and b antigen expression in Le(a-b-) individuals. Blood 1991; 77: 1389-96.
30. Goupille C, Marionneau S, Bureau V, et al. α(1,2)fucosyltransferase increases resistance to apoptosis of rat colon carcinoma cells. Glycobiology 2000; 10: 375-82.
31. Chandrasekaran EV, Jain RK, Rhodes JM, et al. Expression of blood group Lewis b determinant from Lewis a: association of this novel α(1,2)-L-fucosylating activity with the Lewis type α(1,3/4)-L-fucosyltransferase. Biochemistry 1995; 34: 4748-56.
32. Nakamura JI, Mogi A, Asao T, et al. Evidence that the aberrant (1,2)fucosyltransferase found in colorectal carcinoma may be encoded by FUT III (Le gene). Anticancer Res 1997; 17: 4563-69.
33. Yazawa S, Nakamura J, Asao T, et al. Aberrant α1→2fucosyltransferase found in human colorectal carcinoma involved in the accumulation of Leb and Y antigens in colorectal tumors. Jpn J Cancer Res 1993; 84: 989-95.
34. Yazawa S, Nishimura T, Ide M, et al. Tumor-related expression of 1,2fucosylated antigens on colorectal carcinoma cells and its suppression by cell-mediated priming using sugar acceptors for 1,2fucosyltransferase. Glycobiology 2002; 12: 545-53.
35. Ruan S, Lloyd KO. Glycosylation pathways in the biosynthesis of gangliosides in melanoma and neuroblastoma cells: relative glycosyltransferases levels determine ganglioside patterns. Cancer Res 1992; 70: 1467-76.
36. Villar-Portela S, Vázquez-Martín C, Muinelo-Romay L, et al. sLea and sLex expression in colorectal cancer: implications for tumourigenesis and disease prognosis. Histol Histopathol 2011; 26: 1305-16.
37. Kannagi R, Izawa M, Koike T, et al. Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci 2004; 95: 377-84.
38. Sun J, Thurin J, Cooper HS, et al. Elevated expression of H-type GDP-L-fucose:β-D-galactoside α-2-L-fucosyltransferase is associated with human colon-adenocarcinoma progression. Proc Natl Acad Sci 1995; 92: 5724-8.
39. Yazawa S, Madiyalakan R, Izawa H, et al. Cancer-associated elevation of (1,3)activity in human serum. Cancer 1988; 62: 516-20.
40. Nakagoe T, Fukushima K, Hirota M, et al. An immunohistochemical study of the distribution of blood group substances and related antigens in primary colorectal carcinomas and metastatic lymph node and liver lesions, using antibodies against A, B, H type 2, Le(a), and Le(x) antigens. J Gastroenterol 1994; 29: 265-75.
41. Cordon-Cardo C, Lloyd K.O, Sakamoto J, et al. Immunohistologic expression of blood-group antigens in normal human gastrointestinal tract and colonic carcinoma. Int J Cancer 1986; 37: 667-76.
42. Bara J, Mollicone R, Herreo-Zabaleta E, et al. Ectopic expression of the Y (Ley) antigen defined by monoclonal antibody 12-4LE in distal colonic adenocarcinomas. Int J Cancer 1988; 41: 683-9.
43. Hakomori S, Nudelman E, Levery SB, et al. Novel fucolipids accumulating in human adenocarcinoma. I. Glicolipids with di- or tri- fucosylated type 2 chain. J Biol Chem 1984; 259: 4672-80.
44. Cooper HS, Malecha MJ, Bass C, et al. Expression of blood group antigens H-2, Ley, and sialylated-Lea in human colorectal carcinoma. Am J Pathol 1991; 138: 103-10.
45. Prokopishyn NL, Puzon-McLaughlin W, Takada Y, et al. Integrin alpha3beta1 expressed by human colon cancer cells is a major carrier of oncodevelopmental carbohydrate epitopes. J Cell Biochem 1999; 72: 189-209.
46. Trail PA, Willner D, Bianchi AB, et al. Enhanced antitumor activity of paclitaxel in combination with the anticarcinoma immunoconjugate BR96-doxorubicin. Clin Cancer Res 1999; 5: 3632-8.
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Publication history

Received: 26/03/2015

Accepted: 09/06/2015

Online First: 23/06/2015

Published: 25/09/2015

Article revision time: 62 days

Article Online First time: 89 days

Article editing time: 183 days


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