Browse > Article
http://dx.doi.org/10.4062/biomolther.2011.19.3.267

Syndecan as a Messenger to Link Diabetes and Cancer  

Kim, Sung-Jin (Department of Pharmacology and Toxicology, School of Dentistry, Kyung Hee University)
Raman, Os Sethu (Department of Pharmacology and Toxicology, School of Dentistry, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.19, no.3, 2011 , pp. 267-273 More about this Journal
Abstract
Syndecans are membrane-anchored proteoglycans and implicated in the pathogenesis of cancer progression and metastasis. Syndecans also play important roles in interacting with growth factors, extracellular matrix and other cell surface molecules such as IGF-1 receptor. In the present review, we discuss about the syndecan structure, their role in signaling with other receptors, in addition to its general biology. The emerging roles of syndecans in the pathophysiology of human diseases, especially insulin resistance, diabetes and cancer is discussed.
Keywords
Syndecans; Insulin resistance; Diabetes and cancer;
Citations & Related Records

Times Cited By Web Of Science : 0  (Related Records In Web of Science)
Times Cited By SCOPUS : 0
연도 인용수 순위
  • Reference
1 Calle, E. E. and Kaaks, R. (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat. Rev. Cancer 4, 579-591.   DOI
2 Alexander, C. M., Reichsman, F., Hinkes, M. T., Lincecum, J., Becker, K. A., Cumberledge, S. and Bernfi eld, M. (2000) Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice. Nat. Genet. 25, 329-332.   DOI
3 Alexopoulou, A. N., Multhaupt, H. A. and Couchman, J. R. (2007) Syndecans in wound healing, infl ammation and vascular biology. Int. J. Biochem. Cell Biol. 39, 505-528.   DOI
4 Andrian, E., Grenier, D. and Rouabhia, M. (2005) Porphyromonas gingivalis lipopolysaccharide induces shedding of syndecan-1 expressed by gingival epithelial cells. J. Cell Physiol. 204, 178-183.   DOI
5 Anttonen, A., Kajanti, M., Heikkila, P., Jalkanen, M. and Joensuu, H. (1999) Syndecan-1 expression has prognostic signifi cance in head and neck carcinoma. Br. J. Cancer 79, 558-564.   DOI
6 Yang, Y. X., Hennessy, S. and Lewis, J. D. (2004) Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients. Gastroenterology 127, 1044-1050.   DOI
7 Wang, Z., Telci, D. and Griffi n, M. (2011) Importance of syndecan-4 and syndecan -2 in osteoblast cell adhesion and survival mediated by a tissue transglutaminase-fi bronectin complex. Exp. Cell Res. 317, 367-381.   DOI
8 Wiksten, J. P., Lundin, J., Nordling, S., Lundin, M., Kokkola, A., von Boguslawski, K. and Haglund, C. (2001) Epithelial and stromal syndecan- 1 expression as predictor of outcome in patients with gastric cancer. Int. J. Cancer 95, 1-6.   DOI
9 Woods, A. (2001) Syndecans: transmembrane modulators of adhesion and matrix assembly. J. Clin. Invest. 107, 935-941.   DOI
10 Yang, Y., Macleod, V., Miao, H. Q., Theus, A., Zhan, F., Shaughnessy, J. D., Jr., Sawyer, J., Li, J. P., Zcharia, E., Vlodavsky, I. and Sanderson, R. D. (2007) Heparanase enhances syndecan-1 shedding: a novel mechanism for stimulation of tumor growth and metastasis. J. Biol. Chem. 282, 13326-13333.   DOI
11 Yang, Y. X., Hennessy, S. and Lewis, J. D. (2005) Type 2 diabetes mellitus and the risk of colorectal cancer. Clin. Gastroenterol. Hepatol. 3, 587-594.   DOI
12 Zendehdel, K., Nyren, O., Ostenson, C. G., Adami, H. O., Ekbom, A. and Ye, W. (2003) Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden. J. Natl. Cancer Inst. 95, 1797-1800.   DOI   ScienceOn
13 Smith, M. R., Lee, H. and Nathan, D. M. (2006) Insulin sensitivity during combined androgen blockade for prostate cancer. J. Clin. Endocrinol. Metab. 91, 1305-1308.   DOI
14 Steinfeld, R., Van Den Berghe, H. and David, G. (1996) Stimulation of fi broblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican. J. Cell Biol. 133, 405-416.   DOI
15 Songyang, Z., Fanning, A. S., Fu, C., Xu, J., Marfatia, S. M., Chishti, A. H., Crompton, A., Chan, A. C., Anderson, J. M. and Cantley, L. C. (1997) Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science 275, 73-77.   DOI   ScienceOn
16 Soukka, T., Pohjola, J., Inki, P. and Happonen, R. P. (2000) Reduction of syndecan-1 expression is associated with dysplastic oral epithelium. J. Oral Pathol. Med. 29, 308-313.   DOI
17 Stanley, M. J., Stanley, M. W., Sanderson, R. D. and Zera, R. (1999) Syndecan-1 expression is induced in the stroma of infi ltrating breast carcinoma. Am. J. Clin. Pathol. 112, 377-383.   DOI
18 Sun, D., McAlmon, K. R., Davies, J. A., Bernfi eld, M. and Hay, E. D. (1998) Simultaneous loss of expression of syndecan-1 and E-cadherin in the embryonic palate during epithelial-mesenchymal transformation. Int. J. Dev. Biol. 42, 733-736.
19 Tkachenko, E., Rhodes, J. M. and Simons, M. (2005) Syndecans: new kids on the signaling block. Circ. Res. 96, 488-500.   DOI
20 Verheus, M., Peeters, P. H., Rinaldi, S., Dossus, L., Biessy, C., Olsen, A., Tjonneland, A., Overvad, K., Jeppesen, M., Clavel-Chapelon, F., Tehard, B., Nagel, G., Linseisen, J., Boeing, H., Lahmann, P. H., Arvaniti, A., Psaltopoulou, T., Trichopoulou, A., Palli, D., Tumino, R., Panico, S., Sacerdote, C., Sieri, S., van Gils, C. H., Bueno-de- Mesquita, B. H., Gonzalez, C. A., Ardanaz, E., Larranaga, N., Garcia, C. M., Navarro, C., Quiros, J. R., Key, T., Allen, N., Bingham, S., Khaw, K. T., Slimani, N., Riboli, E. and Kaaks, R. (2006) Serum C-peptide levels and breast cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int. J. Cancer 119, 659-667.   DOI
21 Pulkkinen, J. O., Penttinen, M., Jalkanen, M., Klemi, P. and Grenman, R. (1997) Syndecan-1: a new prognostic marker in laryngeal cancer. Acta Otolaryngol. 117, 312-315.   DOI
22 Nakanishi, K., Yoshioka, N., Oka, K. and Hakura, A. (1999) Reduction of syndecan-1 mRNA in cervical-carcinoma cells is involved with the 3' untranslated region. Int. J. Cancer 80, 527-532.   DOI
23 Numa, F., Hirabayashi, K., Kawasaki, K., Sakaguchi, Y., Sugino, N., Suehiro, Y., Suminami, Y., Hirakawa, H., Umayahara, K., Nawata, S., Ogata, H. and Kato, H. (2002) Syndecan-1 expression in cancer of the uterine cervix: association with lymph node metastasis. Int. J. Oncol. 20, 39-43.
24 Perrimon, N. and Bernfi eld, M. (2001) Cellular functions of proteoglycans-- an overview. Semin. Cell Dev. Biol. 12, 65-67.   DOI
25 Purushothaman, A., Chen, L., Yang, Y. and Sanderson, R. D. (2008) Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma. J. Biol. Chem. 283, 32628-32636.   DOI
26 Reizes, O., Goldberger, O., Smith, A. C., Xu, Z., Bernfi eld, M. and Bickel, P. E. (2006) Insulin promotes shedding of syndecan ectodomains from 3T3-L1 adipocytes: a proposed mechanism for stabilization of extracellular lipoprotein lipase. Biochemistry 45, 5703-5711.   DOI
27 Rintala, M., Inki, P., Klemi, P., Jalkanen, M. and Grenman, S. (1999) Association of syndecan-1 with tumor grade and histology in primary invasive cervical carcinoma. Gynecol. Oncol. 75, 372-378.   DOI
28 Sanderson, R. D. (2001) Heparan sulfate proteoglycans in invasion and metastasis. Semin. Cell Dev. Biol. 12, 89-98.   DOI
29 Sanderson, R. D. and Borset, M. (2002) Syndecan-1 in B lymphoid malignancies. Ann. Hematol. 81, 125-135.   DOI
30 Kumar-Singh, S., Jacobs, W., Dhaene, K., Weyn, B., Bogers, J., Weyler, J. and Van Marck, E. (1998) Syndecan-1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome. J. Pathol. 186, 300-305.   DOI
31 Levy, P., Munier, A., Baron-Delage, S., Chastre, E., Gespach, C., Capeau, J. and Cherqui, G. (1997) [Oncogenic activation of p21ras or pp60c-src in human colonic Caco-2 cells induces post-translation alterations of syndecan-1]. Bull. Cancer 84, 235-237.
32 Levy, P., Munier, A., Baron-Delage, S., Di Gioia, Y., Gespach, C., Capeau, J. and Cherqui, G. (1996) Syndecan-1 alterations during the tumorigenic progression of human colonic Caco-2 cells induced by human Ha-ras or polyoma middle T oncogenes. Br. J. Cancer 74, 423-431.   DOI
33 Li, Q., Park, P. W., Wilson, C. L. and Parks, W. C. (2002) Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial effl ux of neutrophils in acute lung injury. Cell 111, 635-646.   DOI
34 Matsumoto, A., Ono, M., Fujimoto, Y., Gallo, R. L., Bernfi eld, M. and Kohgo, Y. (1997) Reduced expression of syndecan-1 in human hepatocellular carcinoma with high metastatic potential. Int. J. Cancer 74, 482-491.   DOI
35 Monroy, A., Kamath, S., Chavez, A. O., Centonze, V. E., Veerasamy, M., Barrentine, A., Wewer, J. J., Coletta, D. K., Jenkinson, C., Jhingan, R. M., Smokler, D., Reyna, S., Musi, N., Khokka, R., Federici, M., Tripathy, D., DeFronzo, R. A. and Folli, F. (2009) Impaired regulation of the TNF-alpha converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: a new mechanism of insulin resistance in humans. Diabetologia 52, 2169-2181.   DOI
36 Nackaerts, K., Verbeken, E., Deneffe, G., Vanderschueren, B., Demedts, M. and David, G. (1997) Heparan sulfate proteoglycan expression in human lung-cancer cells. Int. J. Cancer 74, 335-345.   DOI
37 Inki, P., Joensuu, H., Grenman, R., Klemi, P. and Jalkanen, M. (1994a) Association between syndecan-1 expression and clinical outcome in squamous cell carcinoma of the head and neck. Br. J. Cancer 70, 319-323.   DOI
38 Hsia, E., Richardson, T. P. and Nugent, M. A. (2003) Nuclear localization of basic fi broblast growth factor is mediated by heparan sulfate proteoglycans through protein kinase C signaling. J. Cell. Biochem. 88, 1214-1225.   DOI
39 Ibrahim, Y. H. and Yee, D. (2004) Insulin-like growth factor-I and cancer risk. Growth Horm. IGF Res. 14, 261-269.   DOI
40 Inki, P. and Jalkanen, M. (1996) The role of syndecan-1 in malignancies. Ann. Med. 28, 63-67.   DOI
41 Inki, P., Stenback, F., Grenman, S. and Jalkanen, M. (1994b) Immunohistochemical localization of syndecan-1 in normal and pathological human uterine cervix. J. Pathol. 172, 349-355.   DOI
42 Kaaks, R., Lukanova, A., Rinaldi, S., Biessy, C., Soderberg, S., Olsson, T., Stenman, U. H., Riboli, E., Hallmans, G. and Stattin, P. (2003) Interrelationships between plasma testosterone, SHBG, IGF-I, insulin and leptin in prostate cancer cases and controls. Eur. J. Cancer Prev. 12, 309-315.   DOI
43 Klatka, J. (2002) Syndecan-1 expression in laryngeal cancer. Eur. Arch. Otorhinolaryngol. 259, 115-118.   DOI
44 Kotsovilis, S., Tseleni-Balafouta, S., Charonis, A., Fourmousis, I., Nikolidakis, D. and Vrotsos, J. A. (2010) Syndecan-1 immunohistochemical expression in gingival tissues of chronic periodontitis patients correlated with various putative factors. J. Periodontal Res. 45, 520-531.
45 Kovalszky, I., Dudas, J., Olah-Nagy, J., Pogany, G., Tovary, J., Timar, J., Kopper, L., Jeney, A. and Iozzo, R. V. (1998) Inhibition of DNA topoisomerase I activity by heparan sulfate and modulation by basic fi broblast growth factor. Mol. Cell Biochem. 183, 11-23.   DOI
46 Grootjans, J. J., Zimmermann, P., Reekmans, G., Smets, A., Degeest, G., Durr, J. and David, G. (1997) Syntenin, a PDZ protein that binds syndecan cytoplasmic domains. Proc. Natl. Acad. Sci. U S A 94, 13683-13688.   DOI
47 Gao, Y., Li, M., Chen, W. and Simons, M. (2000) Synectin, syndecan-4 cytoplasmic domain binding PDZ protein, inhibits cell migration. J. Cell Physiol. 184, 373-379.   DOI
48 Giovannucci, E., Rimm, E. B., Liu, Y. and Willett, W. C. (2004) Height, predictors of C-peptide and cancer risk in men. Int. J. Epidemiol. 33, 217-225.   DOI
49 Granes, F., Urena, J. M., Rocamora, N. and Vilaro, S. (2000) Ezrin links syndecan-2 to the cytoskeleton. J. Cell Sci. 113(Pt 7), 1267-1276.
50 Gunter, M. J., Hoover, D. R., Yu, H., Wassertheil-Smoller, S., Manson, J. E., Li, J., Harris, T. G., Rohan, T. E., Xue, X., Ho, G. Y., Einstein, M. H., Kaplan, R. C., Burk, R. D., Wylie-Rosett, J., Pollak, M. N., Anderson, G., Howard, B. V. and Strickler, H. D. (2008) A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol. Biomarkers Prev. 17, 921-929.   DOI
51 Harman, S. M., Metter, E. J., Blackman, M. R., Landis, P. K. and Carter, H. B. (2000) Serum levels of insulin-like growth factor I (IGFI), IGF-II, IGF-binding protein-3, and prostate-specifi c antigen as predictors of clinical prostate cancer. J. Clin. Endocrinol. Metab. 85, 4258-4265.   DOI
52 Hirabayashi, K., Numa, F., Suminami, Y., Murakami, A., Murakami, T. and Kato, H. (1998) Altered proliferative and metastatic potential associated with increased expression of syndecan-1. Tumour Biol. 19, 454-463.   DOI
53 Hoeben, A., Landuyt, B., Highley, M. S., Wildiers, H., Van Oosterom, A. T. and De Bruijn, E. A. (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol. Rev. 56, 549-580.   DOI
54 Fanning, A. S. and Anderson, J. M. (1996) Protein-protein interactions: PDZ domain networks. Curr. Biol. 6, 1385-1388.   DOI
55 Elenius, V., Gotte, M., Reizes, O., Elenius, K. and Bernfi eld, M. (2004) Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1. J. Biol. Chem. 279, 41928-41935.   DOI
56 Endo, K., Takino, T., Miyamori, H., Kinsen, H., Yoshizaki, T., Furukawa, M. and Sato, H. (2003) Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration. J. Biol. Chem. 278, 40764-40770.   DOI
57 Ethell, I. M., Hagihara, K., Miura, Y., Irie, F. and Yamaguchi, Y. (2000) Synbindin, A novel syndecan-2-binding protein in neuronal dendritic spines. J. Cell Biol. 151, 53-68.   DOI
58 Fears, C. Y. and Woods, A. (2006) The role of syndecans in disease and wound healing. Matrix Biol. 25, 443-456.   DOI
59 Fedarko, N. S., Ishihara, M. and Conrad, H. E. (1989) Control of cell division in hepatoma cells by exogenous heparan sulfate proteoglycan. J. Cell Physiol. 139, 287-294.   DOI
60 Flood, A., Mai, V., Pfeiffer, R., Kahle, L., Remaley, A. T., Lanza, E. and Schatzkin, A. (2007) Elevated serum concentrations of insulin and glucose increase risk of recurrent colorectal adenomas. Gastroenterology 133, 1423-1429.   DOI
61 Fornoni, A., Ijaz, A., Tejada, T. and Lenz, O. (2008) Role of infl ammation in diabetic nephropathy. Curr. Diabetes Rev. 4, 10-17.   DOI
62 Frayling, T. M., Colhoun, H. and Florez, J. C. (2008) A genetic link between type 2 diabetes and prostate cancer. Diabetologia 51, 1757-1760.   DOI
63 Chung, Y. W., Han, D. S., Park, K. H., Eun, C. S., Yoo, K. S. and Park, C. K. (2008) Insulin therapy and colorectal adenoma risk among patients with Type 2 diabetes mellitus: a case-control study in Korea. Dis. Colon Rectum 51, 593-597.   DOI
64 Fujiya, M., Watari, J., Ashida, T., Honda, M., Tanabe, H., Fujiki, T., Saitoh, Y. and Kohgo, Y. (2001) Reduced expression of syndecan-1 affects metastatic potential and clinical outcome in patients with colorectal cancer. Jpn. J. Cancer Res. 92, 1074-1081.   DOI
65 Chan, J. M., Stampfer, M. J., Giovannucci, E., Gann, P. H., Ma, J., Wilkinson, P., Hennekens, C. H. and Pollak, M. (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279, 563-566.   DOI   ScienceOn
66 Chen, L. and Sanderson, R. D. (2009) Heparanase regulates levels of syndecan-1 in the nucleus. PLoS One 4, e4947.   DOI
67 Cohen, A. R., Woods, D. F., Marfatia, S. M., Walther, Z., Chishti, A. H. and Anderson, J. M. (1998) Human CASK/LIN-2 binds syndecan-2 and protein 4.1 and localizes to the basolateral membrane of epithelial cells. J. Cell Biol. 142, 129-138.   DOI
68 Conejo, J. R., Kleeff, J., Koliopanos, A., Matsuda, K., Zhu, Z. W., Goecke, H., Bicheng, N., Zimmermann, A., Korc, M., Friess, H. and Buchler, M. W. (2000) Syndecan-1 expression is up-regulated in pancreatic but not in other gastrointestinal cancers. Int. J. Cancer 88, 12-20.   DOI
69 Couchman, J. R. (2003) Syndecans: proteoglycan regulators of cellsurface microdomains? Nat. Rev. Mol. Cell Biol. 4, 926-937.   DOI
70 Couchman, J. R., Chen, L. and Woods, A. (2001) Syndecans and cell adhesion. Int. Rev. Cytol. 207, 113-150.   DOI
71 Cowey, S. and Hardy, R. W. (2006) The metabolic syndrome: A highrisk state for cancer? Am. J. Pathol. 169, 1505-1522.   DOI
72 Beauvais, D. M. and Rapraeger, A. C. (2004) Syndecans in tumor cell adhesion and signaling. Reprod. Biol. Endocrinol. 2, 3.   DOI   ScienceOn
73 Dobra, K., Nurminen, M. and Hjerpe, A. (2003) Growth factors regulate the expression profi le of their syndecan co-receptors and the differentiation of mesothelioma cells. Anticancer Res. 23, 2435-2444.
74 Barbareschi, M., Maisonneuve, P., Aldovini, D., Cangi, M. G., Pecciarini, L., Angelo Mauri, F., Veronese, S., Caffo, O., Lucenti, A., Palma, P. D., Galligioni, E. and Doglioni, C. (2003) High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer 98, 474-483.   DOI
75 Bayer-Garner, I., Dilday, B., Sanderson, R. and Smoller, B. (2001) Acantholysis and spongiosis are associated with loss of syndecan-1 expression. J. Cutan. Pathol. 28, 135-139.   DOI
76 Beauvais, D. M. and Rapraeger, A. C. (2010) Syndecan-1 couples the insulin-like growth factor-1 receptor to inside-out integrin activation. J. Cell Sci. 123, 3796-3807.   DOI
77 Bernfi eld, M., Gotte, M., Park, P. W., Reizes, O., Fitzgerald, M. L., Lincecum, J. and Zako, M. (1999) Functions of cell surface heparan sulfate proteoglycans. Annu. Rev. Biochem. 68, 729-777.   DOI
78 Berster, J. M. and Goke, B. (2008) Type 2 diabetes mellitus as risk factor for colorectal cancer. Arch. Physiol. Biochem. 114, 84-98.   DOI
79 Brockstedt, U., Dobra, K., Nurminen, M. and Hjerpe, A. (2002) Immunoreactivity to cell surface syndecans in cytoplasm and nucleus: tubulin-dependent rearrangements. Exp. Cell Res. 274, 235-245.   DOI
80 Burbach, B. J., Friedl, A., Mundhenke, C. and Rapraeger, A. C. (2003) Syndecan-1 accumulates in lysosomes of poorly differentiated breast carcinoma cells. Matrix Biol. 22, 163-177.   DOI