Advancement of Study on Lewis-Selectin Metastasis Pathway and Anti-Tumor Treatment of Cimetidine in Colorectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Shouxing ¹ , SHANG Peizhong ²

1.Graduate School of Hebei North University, Zhangjiakou 075000, Hebei Province, China;;
2.Department of General Surgery, The 251st Hospital of PLA, Zhangjiakou 075000, Hebei Province, China;

Corresponding author：

Keywords：

Colorectal cancer; Lewis antigen; Selectin; Cimetidine; Metastasis

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Objective To summarize the advancement on Lewis-Selectin metastasis pathway and anti-tumor treatment of cimetidine in colorectal cancer.
Methods Domestic and international publications involving Lewis-Selectin metastasis pathway and antitumor role of cimetidine in recent years were collected and reviewed.
Results The expression of sialyl Lewis X (sLeX) was most significant in Lewis-Selectin metastasis pathway in colorectal cancer. Cancer cells could interact with E-selectin and P-selectin of activated vascular endothelial cells by sLeX ligand on the cell surface, thereby prompting invasion and metastasis. Cimetidine could inhibit the growth of tumor, improve immune response of the host to tumor cell, inhibit angiogenesis of tumor and metastasis. The curative effect of cimetidine on colorectal cancer patients with positive sLeX expression was better than that with negative sLeX expression.
Conclusion Lewis-Selectin metastasis pathway is one of the important metastasis pathway in colorectal cancer. Cimetidine can prevent metastasis of colorectal cancer by blocking sLeX expression.

Citation： WANG Shouxing ,SHANG Peizhong. Advancement of Study on Lewis-Selectin Metastasis Pathway and Anti-Tumor Treatment of Cimetidine in Colorectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(7): 760-764. doi: Copy

1.	尚培中, 张金江, 刘景章, 等. 基质金属蛋白酶26和唾液酸化LewisX蛋白在乳腺癌中的表达及其意义 [J]. 中国普外基础与临床杂志, 2008; 15(7): 474476.
2.	Kobayashi K, Matsumoto S, Morishima T, et al. Cimetidine inhibits cancer cell adhesion to endothelial cells and prevents metastasis by blocking Eselectin expression [J]. Cancer Res, 2000; 60(14): 39783984.
3.	Tsuboi K, Asao T, Ide M, et al. α1, 2 fucosylation is a superior predictor of postoperative prognosis for colorectal cancer compared with blood group A, B, or sialyl Lewis X antigen generated within colorectal tumor tissues [J]. Ann Surg Oncol, 2007; 14(6): 18801889.
4.	Nonaka M, Ma BY, Murai R, et al. Glycosylationdependent interactions of Ctype lectin DCSIGN with colorectal tumorassociated Lewis glycans impair the function and differentiation of monocytederived dendritic cell [J]. J Immunol, 2008; 180(5): 33473356.
5.	BenDavid T, SagiAssif O, Meshel T, et al. The involvement of the sLea selectin ligand in the extravasation of human colorectal carcinoma cells [J]. Immunol Lett, 2008; 116(2): 218224.
6.	Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells [J]. Nat Immunol, 2003; 4(4): 330336.
7.	Morgan ME, van Bilsen JH, Bakker AM, et al. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans [J]. Hum Immunol, 2005; 66(1): 1320.
8.	李飞飞, 林蓓, 郝莹莹, 等. Lewis y抗体对α1, 2岩藻糖转移酶基因转染后卵巢癌细胞的体外抑制作用 [J]. 细胞与分子免疫学杂志, 2008; 24(3): 267269, 273.
9.	Zhang Z, Sun P, Liu J, et al. Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth [J]. Biochim Biophys Acta, 2008; 1783(2): 287296.
10.	尚培中, 谷化平. 乳腺癌Lewis X和唾液酸化Lewis X表达研究 [J]. 中国现代普通外科进展, 2005; 8(2): 104106.
11.	尚培中, 谷化平, 孙印臣. 唾液酸化Lewis X 在大肠癌中的表达研究 [J]. 中华普通外科杂志, 2001; 16(10): 593594.
12.	谷化平, 尚培中, 倪灿荣. Sialy1 Lewis X, CD44v6和Ecadherin 表达与肝细胞癌转移和预后的关系 [J]. 中华普通外科杂志, 2003; 18(2): 109111.
13.	Kawamura Y, Kawashima R , Fukunaga R, et al. Introduction of Sd (a) carbohydrate antigen in gastrointestinal cancer cells eliminates selectin ligands and inhibits metastasis [J]. Cancer Res, 2005; 65(14): 62206227.
14.	Malagolini N, Santini D, Chiricolo M, et al. Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon [J]. Glycobiology, 2007; 17(7): 688697.
15.	Mantur M, Koper O, Snarska J, et al. Evaluation of PDGFAB and sPselectin concentrations in relation to platelet count in patients with colorectal cancer before and after surgical treatment [J]. Pol Arch Med Wewn, 2008; 118(6): 345350.
16.	ReyesReyes ME, George MD, Roberts JD, et al. PSelectin activates integrinmediated colon carcinoma cell adhesion to fibronectin [J]. Exp Cell Res, 2006; 312(20): 40564069.
17.	Uner A, Akcali Z, Unsal D. Serum levels of soluble Eselectin in colorectal cancer [J]. Neoplasma, 2004; 51(4): 269274.
18.	DymickaPiekarska V, Kemona H. Does colorectal cancer clinical advancement affect adhesion molecules (sPselectin, sEselectin and ICAM1) concentration? [J]. Thromb Res, 2009; 124(1): 8083.
19.	郎伟思, 王继见, 张杨眉. Eselectin 在大肠癌的表达及其在血行转移中的作用初探 [J]. 重庆医科大学学报, 2009; 34(7): 867869.
20.	Kannagi R, Izawa M, Koike T, et al. Carbohydratemediated cell adhesion in cancer metastasis and angiogenesis [J]. Cancer Sci, 2004; 95(5): 377384.
21.	Chen AJ, Li Y, Yang GL, et al. Perioperative cimetidine administration enhances tumor infiltration lymphocytes and HLADR expression in colorectal cancer [J]. ChineseGerman Clin Oncol, 2006; 5(1): 4953.
22.	尚培中, 贾国洪, 李晓武, 等. 西咪替丁对大肠癌肝转移的预防和辅助治疗价值 [J/CD]. 中华普外科手术学杂志(电子版), 2009; 3(2): 5356.
23.	Chihara Y, Fujimoto K, Miyake M, et al. Antitumor effect of cimetidine via inhibiting angiogenesis factors in NbutylN(4hydroxybutyl) nitrosamineinduced mouse and rat bladder carcinogenesis [J]. Oncol Rep, 2009; 22(1): 2328.
24.	Bolton E, King J, Morris DL. H2antagonists in the treatment of colon and breast cancer [J]. Semin Cancer Biol, 2000; 10(1): 310.
25.	Matsumoto S, Imaeda Y, Umemoto S, et al. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl LewisX and sialyl LewisA epitope expression on tumour cells [J]. Br J Cancer, 2002; 86(2): 161167.
26.	Tatokoro M, Fujii Y, Kawakami S, et al. Favorable response to combination treatment of cimetidine, cyclooxygenase2 inhibitor and reninangiotensin system inhibitor in metastatic renal cell carcinoma: Reort of three cases [J]. Int J Uol, 2008; 15(9): 848850.
27.	Mathes RW, Malone KE, Daling JR, et al. Relationship between histamine2receptor antagonist medications and risk of invasive breast cancer [J]. Cancer Epidemiol Biomarkers Prev, 2008; 17(1): 6772.
28.	Furuta K, Sato S, Miyake T, et al. Antitumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosaminetreated rats [J]. Oncol Rep, 2008; 19(2): 361368.
29.	Rajendra S, Mulcahy H, Patchett S, et al. The effect of H2 antagonistson proliferation and apoptosis in human colorectal cancer cell lines [J]. Dig Dis Sci, 2004; 49(10): 16341640.
30.	Fujikawa T, Shiraha H, Nakanishi Y, et al. Cimetidine inhibits epidermal growth factorinduced cell signaling [J]. J Gastroenterol Hepatol, 2007; 22(3): 436443.
31.	Fukuda M, Kusama K, Sakashita H. Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression [J]. BMC Cancer, 2008; 8(12): 376389.
32.	Adams WJ, Morris DL. Shortcourse cimetidine and survival with colorectal cancer [J]. Lancet, 1994; 344 (89398940):17681769.
33.	潘永成, 张寿熙, 丁显仲, 等. 甲氰咪胍对创伤大鼠的免疫调节作用 [J]. 中华实验外科杂志, 1996; 13(5): 103104.
34.	Li Y, Yang GL, Yuan HY, et al. Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial [J]. Hepatogastroenterology, 2005; 52(62): 504508.
35.	Takahashi K, Tanaka S, Ichikawa A. Effect of cimetidine on intratumoral cytokine expression in an experimental tumor [J]. Biochem Biophys Research Commun, 2001; 281(5): 11131119.
36.	Asakage M, Tsuno NH, Kitayama J, et al. The effect of cimetidine mainly increases CD4+ cell of peripheral blood T lymphocytes [J]. Gan To Kagaku Ryoho, 2005; 32(11): 15761577.
37.	Bobek V, Boubelik M, Kovarík J, et al. Inhibition of adhesion breast cancer cells by anticoagulant drugs and cimetidine [J]. Neoplasma, 2003; 50(2): 148151.
38.	Tozawa K, Okamoto T, Kawai N, et al. Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma [J]. Kidney Int, 2005; 67(4): 13911396.
39.	Hansbrough JF, ZapataSirvent RL, Bender EM. Prevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen [J]. Am J Surg, 1986; 151(2): 249255.
40.	Lefranc F, Yeaton P, Brotchi J, et al. Cimetidine, an unexpected antitumor agent, and its potential for the treatment of glioblastoma (review) [J]. Int J Oncol, 2006; 28(5): 10211030.
41.	Kawase J, Ozawa S, Kobayashi K, et al. Increase in Eselectin expression in umbilical vein endothelial cells by anticancer drugs and inhibition by cimetidine [J]. Oncol Rep, 2009; 22(6): 12931297.
42.	尚培中, 贾国洪, 苗建军, 等. 西咪替丁预防大肠癌复发转移临床疗效观察 [J/CD]. 中华普通外科学文献(电子版), 2009; 3(1): 2730.

1. 尚培中, 张金江, 刘景章, 等. 基质金属蛋白酶26和唾液酸化LewisX蛋白在乳腺癌中的表达及其意义 [J]. 中国普外基础与临床杂志, 2008; 15(7): 474476.
2. Kobayashi K, Matsumoto S, Morishima T, et al. Cimetidine inhibits cancer cell adhesion to endothelial cells and prevents metastasis by blocking Eselectin expression [J]. Cancer Res, 2000; 60(14): 39783984.
3. Tsuboi K, Asao T, Ide M, et al. α1, 2 fucosylation is a superior predictor of postoperative prognosis for colorectal cancer compared with blood group A, B, or sialyl Lewis X antigen generated within colorectal tumor tissues [J]. Ann Surg Oncol, 2007; 14(6): 18801889.
4. Nonaka M, Ma BY, Murai R, et al. Glycosylationdependent interactions of Ctype lectin DCSIGN with colorectal tumorassociated Lewis glycans impair the function and differentiation of monocytederived dendritic cell [J]. J Immunol, 2008; 180(5): 33473356.
5. BenDavid T, SagiAssif O, Meshel T, et al. The involvement of the sLea selectin ligand in the extravasation of human colorectal carcinoma cells [J]. Immunol Lett, 2008; 116(2): 218224.
6. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells [J]. Nat Immunol, 2003; 4(4): 330336.
7. Morgan ME, van Bilsen JH, Bakker AM, et al. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans [J]. Hum Immunol, 2005; 66(1): 1320.
8. 李飞飞, 林蓓, 郝莹莹, 等. Lewis y抗体对α1, 2岩藻糖转移酶基因转染后卵巢癌细胞的体外抑制作用 [J]. 细胞与分子免疫学杂志, 2008; 24(3): 267269, 273.
9. Zhang Z, Sun P, Liu J, et al. Suppression of FUT1/FUT4 expression by siRNA inhibits tumor growth [J]. Biochim Biophys Acta, 2008; 1783(2): 287296.
10. 尚培中, 谷化平. 乳腺癌Lewis X和唾液酸化Lewis X表达研究 [J]. 中国现代普通外科进展, 2005; 8(2): 104106.
11. 尚培中, 谷化平, 孙印臣. 唾液酸化Lewis X 在大肠癌中的表达研究 [J]. 中华普通外科杂志, 2001; 16(10): 593594.
12. 谷化平, 尚培中, 倪灿荣. Sialy1 Lewis X, CD44v6和Ecadherin 表达与肝细胞癌转移和预后的关系 [J]. 中华普通外科杂志, 2003; 18(2): 109111.
13. Kawamura Y, Kawashima R , Fukunaga R, et al. Introduction of Sd (a) carbohydrate antigen in gastrointestinal cancer cells eliminates selectin ligands and inhibits metastasis [J]. Cancer Res, 2005; 65(14): 62206227.
14. Malagolini N, Santini D, Chiricolo M, et al. Biosynthesis and expression of the Sda and sialyl Lewis x antigens in normal and cancer colon [J]. Glycobiology, 2007; 17(7): 688697.
15. Mantur M, Koper O, Snarska J, et al. Evaluation of PDGFAB and sPselectin concentrations in relation to platelet count in patients with colorectal cancer before and after surgical treatment [J]. Pol Arch Med Wewn, 2008; 118(6): 345350.
16. ReyesReyes ME, George MD, Roberts JD, et al. PSelectin activates integrinmediated colon carcinoma cell adhesion to fibronectin [J]. Exp Cell Res, 2006; 312(20): 40564069.
17. Uner A, Akcali Z, Unsal D. Serum levels of soluble Eselectin in colorectal cancer [J]. Neoplasma, 2004; 51(4): 269274.
18. DymickaPiekarska V, Kemona H. Does colorectal cancer clinical advancement affect adhesion molecules (sPselectin, sEselectin and ICAM1) concentration? [J]. Thromb Res, 2009; 124(1): 8083.
19. 郎伟思, 王继见, 张杨眉. Eselectin 在大肠癌的表达及其在血行转移中的作用初探 [J]. 重庆医科大学学报, 2009; 34(7): 867869.
20. Kannagi R, Izawa M, Koike T, et al. Carbohydratemediated cell adhesion in cancer metastasis and angiogenesis [J]. Cancer Sci, 2004; 95(5): 377384.
21. Chen AJ, Li Y, Yang GL, et al. Perioperative cimetidine administration enhances tumor infiltration lymphocytes and HLADR expression in colorectal cancer [J]. ChineseGerman Clin Oncol, 2006; 5(1): 4953.
22. 尚培中, 贾国洪, 李晓武, 等. 西咪替丁对大肠癌肝转移的预防和辅助治疗价值 [J/CD]. 中华普外科手术学杂志(电子版), 2009; 3(2): 5356.
23. Chihara Y, Fujimoto K, Miyake M, et al. Antitumor effect of cimetidine via inhibiting angiogenesis factors in NbutylN(4hydroxybutyl) nitrosamineinduced mouse and rat bladder carcinogenesis [J]. Oncol Rep, 2009; 22(1): 2328.
24. Bolton E, King J, Morris DL. H2antagonists in the treatment of colon and breast cancer [J]. Semin Cancer Biol, 2000; 10(1): 310.
25. Matsumoto S, Imaeda Y, Umemoto S, et al. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl LewisX and sialyl LewisA epitope expression on tumour cells [J]. Br J Cancer, 2002; 86(2): 161167.
26. Tatokoro M, Fujii Y, Kawakami S, et al. Favorable response to combination treatment of cimetidine, cyclooxygenase2 inhibitor and reninangiotensin system inhibitor in metastatic renal cell carcinoma: Reort of three cases [J]. Int J Uol, 2008; 15(9): 848850.
27. Mathes RW, Malone KE, Daling JR, et al. Relationship between histamine2receptor antagonist medications and risk of invasive breast cancer [J]. Cancer Epidemiol Biomarkers Prev, 2008; 17(1): 6772.
28. Furuta K, Sato S, Miyake T, et al. Antitumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosaminetreated rats [J]. Oncol Rep, 2008; 19(2): 361368.
29. Rajendra S, Mulcahy H, Patchett S, et al. The effect of H2 antagonistson proliferation and apoptosis in human colorectal cancer cell lines [J]. Dig Dis Sci, 2004; 49(10): 16341640.
30. Fujikawa T, Shiraha H, Nakanishi Y, et al. Cimetidine inhibits epidermal growth factorinduced cell signaling [J]. J Gastroenterol Hepatol, 2007; 22(3): 436443.
31. Fukuda M, Kusama K, Sakashita H. Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression [J]. BMC Cancer, 2008; 8(12): 376389.
32. Adams WJ, Morris DL. Shortcourse cimetidine and survival with colorectal cancer [J]. Lancet, 1994; 344 (89398940):17681769.
33. 潘永成, 张寿熙, 丁显仲, 等. 甲氰咪胍对创伤大鼠的免疫调节作用 [J]. 中华实验外科杂志, 1996; 13(5): 103104.
34. Li Y, Yang GL, Yuan HY, et al. Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial [J]. Hepatogastroenterology, 2005; 52(62): 504508.
35. Takahashi K, Tanaka S, Ichikawa A. Effect of cimetidine on intratumoral cytokine expression in an experimental tumor [J]. Biochem Biophys Research Commun, 2001; 281(5): 11131119.
36. Asakage M, Tsuno NH, Kitayama J, et al. The effect of cimetidine mainly increases CD4+ cell of peripheral blood T lymphocytes [J]. Gan To Kagaku Ryoho, 2005; 32(11): 15761577.
37. Bobek V, Boubelik M, Kovarík J, et al. Inhibition of adhesion breast cancer cells by anticoagulant drugs and cimetidine [J]. Neoplasma, 2003; 50(2): 148151.
38. Tozawa K, Okamoto T, Kawai N, et al. Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma [J]. Kidney Int, 2005; 67(4): 13911396.
39. Hansbrough JF, ZapataSirvent RL, Bender EM. Prevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen [J]. Am J Surg, 1986; 151(2): 249255.
40. Lefranc F, Yeaton P, Brotchi J, et al. Cimetidine, an unexpected antitumor agent, and its potential for the treatment of glioblastoma (review) [J]. Int J Oncol, 2006; 28(5): 10211030.
41. Kawase J, Ozawa S, Kobayashi K, et al. Increase in Eselectin expression in umbilical vein endothelial cells by anticancer drugs and inhibition by cimetidine [J]. Oncol Rep, 2009; 22(6): 12931297.
42. 尚培中, 贾国洪, 苗建军, 等. 西咪替丁预防大肠癌复发转移临床疗效观察 [J/CD]. 中华普通外科学文献(电子版), 2009; 3(1): 2730.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Advancement of Study on Lewis-Selectin Metastasis Pathway and Anti-Tumor Treatment of Cimetidine in Colorectal Cancer

Abstract Full text Figures/Tables Video References Cited by

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