Soluble N-cadherin in human biological fluids
Lara Derycke
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorOlivier De Wever
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorVeronique Stove
Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorBarbara Vanhoecke
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
Department of Gynaecological Oncology, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorJoris Delanghe
Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorHerman Depypere
Department of Gynaecological Oncology, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorCorresponding Author
Marc Bracke
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
Fax: +32-92404991
Laboratory of Experimental Cancerology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, BelgiumSearch for more papers by this authorLara Derycke
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorOlivier De Wever
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorVeronique Stove
Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorBarbara Vanhoecke
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
Department of Gynaecological Oncology, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorJoris Delanghe
Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorHerman Depypere
Department of Gynaecological Oncology, Ghent University Hospital, Ghent, Belgium
Search for more papers by this authorCorresponding Author
Marc Bracke
Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
Fax: +32-92404991
Laboratory of Experimental Cancerology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, BelgiumSearch for more papers by this authorAbstract
Classical cadherins such as E-, P- and N-cadherin are transmembrane proteins that mediate cell–cell adhesion, and are important in embryogenesis, maintenance of tissue integrity and cancer. Proteolytic shedding of the extracellular domain results in the generation of soluble E-, P- or N-cadherin ectodomains. Circulating soluble E- and P-cadherin have been described in the serum, and elevated levels were detected in cancer patients when compared with healthy persons. Here we report the presence of soluble N-cadherin, a 90-kD protein fragment, in the serum of both healthy persons and cancer patients, using a direct ELISA and immunoprecipitation. A correlation was found between prostate specific antigen and soluble N-cadherin, and significantly elevated levels were detected in prostate cancer follow-up patients. The N-cadherin protein is neo-expressed by carcinomas of the prostate, and is responsible for epithelial to fibroblastic transition. This is reflected by the higher concentrations of soluble N-cadherin in prostate cancer patients than in healthy persons. © 2006 Wiley-Liss, Inc.
References
- 1 Jaggi M, Nazemi T, Abrahams NA, Baker JJ, Galich A, Smith LM, Balaji KC. N-cadherin switching occurs in high Gleason grade prostate cancer. Prostate 2006; 66: 193–9.
- 2 Paredes J, Milanezi F, Viegas L, Amendoeira I, Schmitt F. P-cadherin expression is associated with high-grade ductal carcinoma in situ of the breast. Virchows Arch 2002; 440: 16–21.
- 3 Tomita K, van Bokhoven A, van Leenders GJLH, Ruijter ETG, Jansen CFJ, Bussemakers MJG, Schalken JA. Cadherin switching in human prostate cancer progression. Cancer Res 2000; 60: 3650–4.
- 4 Derycke LDM, Bracke ME. N-cadherin in the spotlight of cell–cell adhesion, differentiation, embryogenesis, invasion and signalling. Int J Dev Biol 2004; 48: 463–76.
- 5 Noë V, Bruyneel E, Mareel M, Bracke M. The E-cadherin/catenin complex in invasion: the role of ectodomain shedding. In: WG Jiang, RE Mansel, eds. Cancer metastasis, molecular and cellular mechanisms and clinical intervention. Dordrecht, The Netherlands: Kluwer, 2000. 73–119.
- 6 Davies G, Jiang WG, Mason MD. Matrilysin mediates extracellular cleavage of E-cadherin from prostate cancer cells: a key mechanism in hepatocyte growth factor/scatter factor-induced cell–cell dissociation and in vitro invasion. Clin Cancer Res 2001; 7: 3289–97.
- 7 Ryniers F, Stove C, Goethals M, Brackenier L, Noë V, Bracke M, Vandekerckhove J, Mareel M, Bruyneel E. Plasmin produces an E-cadherin fragment that stimulates cancer cell invasion. Biol Chem 2002; 383: 159–65.
- 8 Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, de Strooper B, Hartmann D, Saftig P. ADAM10 mediates E-cadherin shedding and regulates epithelial cell–cell adhesion, migration, and β-catenin translocation. Proc Natl Acad Sci USA 2005; 102: 9182–7.
- 9 Paradies NE, Grunwald GB. Purification and characterization of NCAD90, a soluble endogenous form of N-cadherin, which is generated by proteolysis during retinal development and retains adhesive and neurite-promoting function. J Neurosci Res 1993; 36: 33–45.
- 10 Derycke L, Morbidelli L, Ziche M, De Wever O, Bracke M, Van Aken E. Soluble N-cadherin fragment promotes angiogenesis. Clin Exp Metastasis, In press, DOI: 10.1007/s10585-006-9029-7
- 11 Reiss K, Maretzky T, Ludwig A, Tousseyn T, de Strooper B, Hartmann D, Saftig P. ADAM10 cleavage of N-cadherin and regulation of cell–cell adhesion and β-catenin nuclear signalling. EMBO J 2005; 24: 742–52.
- 12 Covington MD, Burghardt RC, Parrish AR. Ischemia-induced cleavage of cadherins in NRK cells requires MT1-MMP (MMP-14). Am J Physiol Renal Physiol 2006; 290: F43–F51.
- 13 Monea S, Jordan BA, Srivastava S, DeSouza S, Ziff EB. Membrane localization of membrane type 5 matrix metalloproteinase by AMPA receptor binding protein and cleavage of cadherins. J Neurosci 2006; 26: 2300–12.
- 14 Katayama M, Hirai S, Kamihagi K, Nakagawa K, Yasumoto M, Kato I. Soluble E-cadherin fragments increased in circulation of cancer patients. Br J Cancer 1994; 69: 580–5.
- 15 Chan AOO, Chu K-M, Lam SK, Cheung KL, Law S, Kwok K-F, Wong WM, Yuen MF, Wong BC-Y. Early prediction of tumor recurrence after curative resection of gastric carcinoma by measuring soluble E-cadherin. Cancer 2005; 104: 740–6.
- 16 Banks RE, Porter WH, Whelan P, Smith PH, Selby PJ. Soluble forms of the adhesion molecule E-cadherin in urine. J Clin Pathol 1995; 48: 179, 180.
- 17 Protheroe AS, Banks RE, Mzimba M, Porter WH, Southgate J, Singh PN, Bosomworth M, Harnden P, Smith PH, Whelan P, Selby PJ. Urinary concentrations of the soluble adhesion molecule E-cadherin and total protein in patients with bladder cancer. Br J Cancer 1999; 80: 273–8.
- 18 Shariat SF, Matsumoto K, Casella R, Jian W, Lerner SP. Urinary levels of soluble E-cadherin in the detection of transitional cell carcinoma of the urinary bladder. Eur Urol 2005; 48: 69–76.
- 19 Knudsen KA, Lin CY, Johnson KR, Wheelock MJ, Keshgegian AA, Soler AP. Lack of correlation between serum levels of E- and P-cadherin fragments and the presence of breast cancer. Hum Pathol 2000; 31: 961–5.
- 20 Soler AP, Russo J, Russo IH, Knudsen KA. Soluble fragment of P-cadherin adhesion protein found in human milk. J Cell Biochem 2002; 85: 180–4.
- 21 De Paul AL, Bonaterra M, Soler AP, Knudsen KA, Roth FD, Aoki A. Soluble P-cadherin found in human semen. J Androl 2005; 26: 44–7.
- 22 Rieger-Christ KM, Cain JW, Braasch JW, Dugan JM, Silverman ML, Bouyounes B, Libertino JA, Summerhayes IC. Expression of classic cadherins type I in urothelial neoplastic progression. Hum Pathol 2001; 32: 18–23.
- 23 Nagi C, Guttman M, Jaffer S, Qiao R, Keren R, Triana A, Li M, Godbold J, Bleiweiss IJ, Hazan RB. N-cadherin expression in breast cancer: correlation with an aggressive histologic variant—invasive micropapillary carcinoma. Breast Cancer Res Treat 2005; 94: 225–35.
- 24 De Wever O, Westbroek W, Verloes A, Bloemen N, Bracke M, Gespach C, Bruyneel E, Mareel M. Critical role of N-cadherin in myofibroblast invasion and migration in vitro stimulated by colon-cancer-cell-derived TGF-β or wounding. J Cell Sci 2004; 117: 4691–703.
- 25 Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002; 2: 161–74.
- 26 Mège RM, Matsuzaki F, Gallin WJ, Goldberg JI, Cunningham BA, Edelman GM. Construction of epithelioid sheets by transfection of mouse sarcoma cells with cDNAs for chicken cell adhesion molecules. Proc Natl Acad Sci USA 1998; 85: 7274–8.
- 27 Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 2004; 16: 558–64.
- 28 Riddick ACP, Shukla CJ, Pennington CJ, Bass R, Nuttall RK, Hogan A, Sethia KK, Ellis V, Collins AT, Maitlan NJ, Ball RY, Edwards DR. Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues. Br J Cancer 2005; 92: 2171–80.
- 29 Villanueva J, Shaffer DR, Philip J, Chaparro CA, Erdjument-Bromage H, Olshen AB, Fleisher M, Lilja H, Brogi E, Boyd J, Sanchez-Carbayo M, Holland EC, et al. Differential exoprotease activities confer tumor-specific serum peptidome patterns. J Clin Invest 2006; 116: 271–84.
- 30 Damsky CH, Richa J, Solter D, Knudsen K, Buck CA. Identification and purification of a cell surface glycoprotein mediating intercellular adhesion in embryonic and adult tissue. Cell 1983; 34: 455–66.
- 31 Gofuku J, Shiozaki H, Doki Y, Inoue M, Hirao M, Fukuchi N, Monden M. Characterization of soluble E-cadherin as a disease marker in gastric cancer patients. Br J Cancer 1998; 78: 1095–101.
- 32 Chan AOO, Lam SK, Chu KM, Lam CM, Kwok E, Leung SY, Yuen ST, Law SYK, Hui WM, Lai KC, Wong CY, Hu HC, et al. Soluble E-cadherin is a valid prognostic marker in gastric carcinoma. Gut 2001; 48: 808–11.
- 33 Chan AO-O, Chu K-M, Lam S-K, Wong BC-Y, Kwok K-F, Law S, Ko S, Hui W-M, Yueng Y-H, Wong J. Soluble E-cadherin is an independent pretherapeutic factor for long-term survival in gastric cancer. J Clin Oncol 2003; 21: 2288–93.
- 34 Pittard AJ, Banks RE, Galley HF, Webster NR. Soluble E-cadherin concentrations in patients with systemic inflammatory response syndrome and multiorgan dysfunction syndrome. Br J Anaesth 1996; 76: 629–31.