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YKL-40: A Novel Marker Shared by Chronic Inflammation and Oncogenic Transformation

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Book cover Inflammation and Cancer

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 511))

Summary

YKL-40, a member of ‘mammalian chitinase-like proteins’, is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle-, and cancer cells. High serum YKL-40 is a biomar-ker of poor prognosis in patients with cancer, inflammation and increased tissue remodelling. High YKL-40 protein expression assessed by immunohistochemistry is found in breast carcinomas associated with short disease-free survival and in glioblastomas with increased resistance to radiotherapy and decreased overall survival. In this chapter we describe the methods for the detection of (1) YKL-40 protein expression in human tissues (using immunohistochemistry) and cell cultures (using immunocytochemistry); (2) YKL-40 mRNA expression in human tissues (using in situ hybridization and Polymerase Chain Reaction); and (3) YKL-40 protein concentrations in serum or plasma (using Enzyme-Linked ImmunoSorbent Assay).

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References

  1. Johansen, J.S., Williamson, M.K., Rice, J.S., and Price, P.A. (1992) Identification of proteins secreted by human osteoblastic cells in culture. J. Bone Miner. Res. 7, 501–512

    Article  CAS  PubMed  Google Scholar 

  2. Hakala, B.E., White, C., and Recklies, A.D. (1993) Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J. Biol. Chem. 268, 25803–25810

    CAS  PubMed  Google Scholar 

  3. Shackelton, L.M., Mann, D.M., and Millis, A.J.T. (1995) Identification of a 38-kDa heparin-binding glycoprotein (gp38k) in differentiating vascular smooth muscle cells as a member of a group of proteins associated with tissue remodeling. J. Biol. Chem. 270, 13076–13083

    Article  CAS  PubMed  Google Scholar 

  4. Renkema, G.H., Boot, G.R., Au, F.L., Donker-Koopman W.E., Strijland, A, Muijsers A.O., et al. (1998) Chitotriosidase, a chitinase, and the 39-kDa human cartilage glycoprotein, a chitin-binding lectin, are homologues of family 18 glycosyl hydrolases secreted by human macrophages. Eur. J. Biochem. 251, 504–509

    Article  CAS  PubMed  Google Scholar 

  5. Bigg, H.F., Wait, R., Rowan, A.D., and Caw-ston, T.E. (2006) The mammalian chitinase-like lectin, YKL-40, binds specifically to type I collagen fibril formation. J. Biol. Chem. 281, 21082–21095

    Article  CAS  PubMed  Google Scholar 

  6. Funkhouser, J.D., and Aronson, N.N. (2007) Chitinase family GH18: evolutionary insights from the genomic history of a diverse protein family. BMC Evol. Biol. 7, 96

    Article  PubMed  Google Scholar 

  7. Rehli, M., Niller, H.-H., Ammon, C., Lang-mann, S., Schwarz-Fisher, L., Andreeesen, R., et al. (2003) Transcriptional regulation of CHI3L1, a marker gene for late stages of macrophage differentiation. J. Biol. Chem. 278, 44058–44067

    Article  CAS  PubMed  Google Scholar 

  8. Rehli, M., Krause, S.W., and Andreesen, R. (1997) Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics 43, 221–225

    Article  CAS  PubMed  Google Scholar 

  9. Fusetti, F., Pijning, T., Kalk, K.H., Bos, E., and Dijkstra, B.W. (2003) Crystal structure and carbohydrate binding properties of the human cartilage glycoprotein-39. J. Biol. Chem. 278, 37753–37760

    Article  CAS  PubMed  Google Scholar 

  10. Houston, D.R., Recklies, A.D., Krupa, J.C., and van Aalten, D.M.F. (2003) Structure and ligand-induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes. J. Biol. Chem. 278, 30206– 30212

    Article  CAS  PubMed  Google Scholar 

  11. Junker, N., Johansen, J.S., Hansen, L.T., Lund, E.L., and Kristjansen, P.E.G. (2005) Regulation of YKL-40 expression during gen-otoxic or microenvironmental stress in human glioblastoma cells. Cancer Sci. 96, 183–190

    Article  CAS  PubMed  Google Scholar 

  12. Morrison, B.W., and Leder, P. (1994) neu and ras initiate murine mammary tumors that share genetic markers generally absent in c-myc and int-2-initiated tumors. Oncogene 9, 3417–3426

    CAS  PubMed  Google Scholar 

  13. Johansen, J.S., Høyer, P.E., Larsen, L.A., Price, P.A., and Møllgård, K. (2007) YKL-40 protein expression in the early developing human musculoskeletal system. J. Histochem. Cytochem. 55, 1213–1228

    Article  CAS  PubMed  Google Scholar 

  14. Junker, N., Johansen, J.S., Andersen, C.B., and Kristjansen, P.E.G. (2005) Expression of YKL-40 by peritumoral macrophages in human small cell lung cancer. Lung Cancer 48, 223–231

    Article  PubMed  Google Scholar 

  15. Volck, B., Price, P.A., Johansen, J.S., Sørensen, O., Benfield, T., Calafat, J., et al. (1998) YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Proc. Assoc. Am. Phys. 110, 351–360

    CAS  PubMed  Google Scholar 

  16. Johansen, J.S., Olee, T., Price, P.A., Hashimoto, S., Ochs, R.L., and Lotz, M. (2001) Regulation of YKL-40 production by human articular chondrocytes. Arthritis Rheum. 44, 826–837

    Article  CAS  PubMed  Google Scholar 

  17. Volck, B., Johansen, J.S., Stoltenberg, M., Garbarsch, C., Price, P.A., Østergaard, M., et al. (2001) Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology. Osteoarthr Cartilage 9, 203–214

    Article  CAS  Google Scholar 

  18. Malinda, K.M., Ponce, L., Kleinman, H.K., Shackelton, L.M., and Millis, A.J.T. (1999) Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothe-lial cells. Exp. Cell Res. 250, 168–173

    Article  CAS  PubMed  Google Scholar 

  19. Nishikawa, K.C., and Millis, A.J.T. (2003) gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. Exp. Cell Res. 287, 79–87

    Article  CAS  PubMed  Google Scholar 

  20. Nyirkos, P., and Golds, E.E. (1990) Human synovial cells secrete a 39 kDa protein similar to a bovine mammary protein expressed during the non-lactating period. Biochem. J. 268, 265–268

    Google Scholar 

  21. Dasuri, K., Antonovici, M., Chen, K., Wong, K., Standing, K., Ens, W., et al. (2004) The synovial proteome: analysis of fibroblast-like synoviocytes. Arthritis Res. Ther. 6, R161–168

    Article  CAS  PubMed  Google Scholar 

  22. Ringsholt, M., Høgdall, E.V.S., Johansen, J.S., Price, P.A., and Christensen, L.H. (2007) YKL-40 protein expression in normal human tissues – an immunohistochemical study. J. Mol. Histol. 38, 33–43

    Article  CAS  PubMed  Google Scholar 

  23. Huang, Y., Prasad, M., Lemon, W.J., Hampel, H., Wright, F.A., Kornacker, K., et al. (2001) Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc. Natl. Acad. Sci. U.S.A. 98, 15044–15049

    Article  CAS  PubMed  Google Scholar 

  24. Lal, A., Lash, A.E., Altschul, S.F., Velculescu, V., Zhang, L., McLendon, R.E., et al. (1999) A public database for gene expression in human cancers. Cancer Res. 59, 5403–5407

    CAS  PubMed  Google Scholar 

  25. Markert, J.M., Fuller, C.M., Gillespie, G.Y., Bubien, J.K., McLena, L.A., Hong, R.L., et al. (2001) Differential gene expression profiling in human brain tumors. Physiol. Genom-ics 5, 21–33

    CAS  Google Scholar 

  26. Tanwar, M.K., Gilbert, M.R., and Holland, E.C. (2002) Gene expression microarray analysis reveals YKL-40 to be a potential serum marker for malignant character in human gli-oma. Cancer Res. 62:4364–4368

    CAS  PubMed  Google Scholar 

  27. Nigro, J.M., Misra, A., Zhang, L., Smirnov, I., Colman, H., Griffin, C., et al. (2005) Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of gliob-lastoma. Cancer Res. 65, 1678–1686

    Article  CAS  PubMed  Google Scholar 

  28. Phillips, H.S., Kharbanda, S., Chen, R., Forrest, W.F., Soriano, R.H., Wu, T.D., et al. (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progressin, and resemble stages in neurogenesis. Cancer Cell 9, 157–173

    Article  CAS  PubMed  Google Scholar 

  29. Sjögren, H., Meis-Kindblom, J.M., Örndal, C., Bergh P., Ptaszynski K., Åman P., et al. (2003) Studies on the molecular pathogen-esis of extraskeletal myxoid chondrosarcoma-cytogenetic, molecular genetic, and cDNA microarray analyses. Am. J. Pathol. 162, 781–792

    Article  PubMed  Google Scholar 

  30. Nutt, C.L., Betensky, R.A., Brower, M.A., Batchelor, T.T., Louis, D.N., and Stemmer-Rachamimow, A.O. (2005) YKL-40 is a differential diagnostic marker for histologic subtypes of high-grade gliomas. Clin. Cancer Res. 11, 2258–2264

    Article  CAS  PubMed  Google Scholar 

  31. Pelloski, C.E., Mahajan, A., Maor, M., Chang, E.L., Woo, S., Gilbert, M., et al. (2005) YKL-40 Expression is associated with poorer response to radiation and shorter overall survival in glioblastoma. Clin. Cancer Res. 11, 3326–3334

    Article  CAS  PubMed  Google Scholar 

  32. Pelloski, C.E., Ballman, K.V., Furth, A.F., Zhang, L., Lin, E., Sulman, E.P., et al. (2007) Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J. Clin. Oncol. 25, 2288–2294

    Article  CAS  PubMed  Google Scholar 

  33. Kim, S.H., Das, K., Noreen, S., Coffman, F., Hameed, M. (2007) Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer. World J. Surg. Oncol. 5, 17

    Article  PubMed  Google Scholar 

  34. Roslind, A., Johansen, J.S., Junker, N., Nielsen, D.L., Dzaferi, H., Price, P.A., et al. (2007) YKL-40 expression in benign and malignant breast lesions: A methodological study. Appl. Immunohistochem. Mol. Morphol. 15, 371–381

    Article  CAS  PubMed  Google Scholar 

  35. Roslind, A., Knoop, A.S., Jensen, M.B., Johansen, J.S., Nielsen, D.L., Price, P.A., et al. (2008) YKL-40 Protein expression is not a prog nostic marker in patients with primary breast cancer. Breast Cancer Res.Treat. (in Press)

    Google Scholar 

  36. Lau, S.H., Sham, J.S.T., Xie, D. Tzang, C.H., Tang, D., Ma, N., et al. (2006) Clusterin plays an important role in hepatocellular carcinoma metastasis. Oncogene 25, 1242–1250

    Article  CAS  PubMed  Google Scholar 

  37. Fukushima, N., Koopmann, J., Sato, N., Prasad, N., Carvalho, R., Leach, S.D., et al. (2005) Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma. Mod. Pathol. 18, 779–787

    Article  CAS  PubMed  Google Scholar 

  38. Kirkpatrick, R.B., Matico, R.E., McNulty, D.E., Strickler, J.E., and Rosenberg, M. (1995) An abundantly secreted glycoprotein from Drosophila melanogaster is related to mammalian secretory proteins produced in rheumatoid tissues and by activated macro-phages. Gene 153, 147–154

    Article  CAS  PubMed  Google Scholar 

  39. Kirkpatrick, R.B., Emery, J.G., Connor, J.R., Dodds, R., Lysko, P.G., Rosenberg, M., et al. (1997) Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages. Exp. Cell. Res. 237, 46–54

    Article  CAS  PubMed  Google Scholar 

  40. Baeten, D., Boots, A.M.H., Steenbakkers, P.G.A., Elewaut, D., Bos, E., Verheijden, G.F.M., et al. (2000) Human cartilage gp-39+, CD16+ monocytes in peripheral blood and synovium. Correlation with joint destruction in rheumatoid arthritis. Arthritis Rheum. 43, 1233–1243

    Article  CAS  PubMed  Google Scholar 

  41. Boot, R.G., van Achterberg, T.A.E., van Aken, B.E., Renkema, G.H., Jacobs, M.J.H.M., Aerts, J.M.F.G., et al. (1999) Strong induction of members of the chitinase family of proteins in atherosclerosis. Chitotriosidase and human cartilage gp-39 expressed in lesion macrophages. Arterioscler. Thromb. Vasc. Biol. 19, 687–694

    CAS  PubMed  Google Scholar 

  42. Johansen, J.S., Baslund, B., Garbarsch, C., Hansen, M., Stoltenberg, M., Lorenzen, I., et al. (1999) YKL-40 in giant cells and macro-phages from patients with giant cell arthritis. Arthritis Rheum. 42, 2624–2630

    Article  CAS  PubMed  Google Scholar 

  43. De Ceuninck, F., Gaufillier, S., Bonnaud, A., Sabatini, M., Lesur, C., and Pastoureau, P. (2001) YKL-40 (cartilage gp-39) induces pro- liferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes. Biochem. Biophys. Res. Commun. 285, 926–931

    Article  PubMed  Google Scholar 

  44. Recklies, A.D., White, C., and Ling, H. (2002) The chitinase 3-like protein human cartilage 39 (HC-gp39) stimulates prolif eration of human connective-tissue cells and activates both extracellular signal-regulated kinase-and protein kinase B-mediated signal ling pathways. Biochem. J. 365, 119–126

    Article  CAS  PubMed  Google Scholar 

  45. Ling, H., and Recklies, A.D. (2004) The chi-tinase 3-like protein human cartilage glyco-protein 39 inhibits cellular responses to the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha. Biochem. J. 380, 651–659

    Article  CAS  PubMed  Google Scholar 

  46. Recklies, A.D., Ling, H., White, C., and Bernier, S.M. (2005) Inflammatory cytokines induce production of CHI3L1 by articular chondro-cytes. J. Biol. Chem. 280, 41213–41221

    Article  CAS  PubMed  Google Scholar 

  47. Verheiden, G.F.M., Rijnders, A.W.M., Bos, E., Coenen-de ROO, C.J.J., van Staveren C.J., Miltenburg, A.M.M., et al. (1997) Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis. Arthritis Rheum. 40: 1115–1125

    Article  Google Scholar 

  48. Tsark, E.C., Wang, W., Teng, Y.C., Arkfeld, D., Dodge, G.R., and Kovats, S. (2002) Differential MHC class II-mediated presentation of rheumatoid arthritis autoantigens by human dendritic cells and macrophages. J. Immunol. 169, 6625–6633

    CAS  PubMed  Google Scholar 

  49. Mizoguchi, E. (2006) Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells. Gastroenterology 130, 398–411

    Article  CAS  PubMed  Google Scholar 

  50. Mizoguchi, E., and Mizoguchi, A. (2007) Is the sugar always sweet in intestinal inflammation? Immunol. Res. 37, 47–60

    Article  CAS  PubMed  Google Scholar 

  51. Nordenbaek, C., Johansen, J.S., Junker, P., Bor-regaard, N., Sørensen, O., Price, P.A. (1999) YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hos-pitalization. J. Infect. Dis. 180, 1722–1726

    Article  CAS  PubMed  Google Scholar 

  52. Kronborg, G., Østergaard, C., Weis, N., Nielsen, H., Obel, N., Pedersen, S.S., et al. (2002) Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacter-emia and is associated with the outcome of the disease. Scand. J. Infect. Dis. 34, 323–326

    Article  PubMed  Google Scholar 

  53. Johansen, J.S., Krabbe, K., Møller, K., and Pedersen, B.K. (2005) Circulating YKL-40 levels during human endotoxaemia. Clin. Exp. Immunol. 140, 343–348

    Article  CAS  PubMed  Google Scholar 

  54. Johansen, J.S. (2006) Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibrosis and cancer. Dan. Med. Bull. 53, 172–209

    CAS  PubMed  Google Scholar 

  55. Harvey, S., Weisman, M., O'Dell, J., Scott, T., Krusemeier, M., Visor, J., et al. (1998) Chon-drex: new marker of joint disease. Clin. Chem. 44, 509–516

    CAS  PubMed  Google Scholar 

  56. Koutroubakis, I.E., Petinaki, E., Dimoulios, P., Vardas, E., Roussomoustakaki, M., Maniatis, A.N., et al. (2003) Increased serum levels of YKL-40 in patients with inflammatory bowel disease. Int. J. Colorectal. Dis. 18, 254–259

    PubMed  Google Scholar 

  57. Vind, I., Johansen, J.S., Price, P.A., and Munkholm, P. (2003) Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease. Scand. J. Gastroenterol. 38, 599–605

    Article  CAS  PubMed  Google Scholar 

  58. Rathcke, C.N., Johansen, J.S., and Vester-gaard, H. (2006) YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance. Inflamm. Res. 55, 53–59

    Article  CAS  PubMed  Google Scholar 

  59. Kucur, M., Isman, F.K., Karadag, B., Vural, V.A., and Tavsanoglu, S. (2007) Serum YKL-40 levels in patients with coronary artery disease. Coron. Artery. Dis. 18, 391–396

    Article  PubMed  Google Scholar 

  60. Nøjgaard, C., Høst, N.B., Christensen, I.J., Poulsen, S.H., Egstrup, K., Price, P.A., et al. (2007) Serum levels of YKL-40 increases in patients with acute myocardial infarction. Coron. Artery. Dis. (submitted)

    Google Scholar 

  61. Johansen, J.S., Milman, N., Hansen, M., Gar-barsch, C., Price, P.A., and Graudal, N. (2005) Increased serum YKL-40 in patients with pulmonary sarcoidosis. A potential marker of disease activity? Respir. Med. 99, 396–402

    Article  PubMed  Google Scholar 

  62. Johansen, J.S., Christoffersen, P., Møller, S., Price, P.A., Henriksen, J.H., Garbarsch, C., et al. (2000) Serum YKL-40 is increased in patients with hepatic fibrosis. J. Hepatol. 32, 911–920

    Article  CAS  PubMed  Google Scholar 

  63. Tran, A., Benzaken, S., Saint-Paul, M.-C., Guzman-Granier, E., Hastier, P., Pradier, C., et al. (2000) Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease. Eur. J. Gastroenterol. Hepatol. 12, 989–993

    Article  CAS  PubMed  Google Scholar 

  64. Nøjgaard, C., Johansen, J.S., Christensen, E., Skovgaard, L.T., Price, P.A., Becker, U. and The EMALD Group (2003) Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease. J. Hepa-tol. 39, 179–186

    Article  Google Scholar 

  65. Nøjgaard, C., Johansen, J.S., Krarup, H.B., Holten-Andersen, M., Møller, A., Bendtsen, F. and the Danish Viral Hepatitis Study Group (2003) Effect of antiviral therapy on markers of fibrogenesis in patients with chronic hepatitis C. Scand. J. Gastroenterol. 38, 659–665

    Article  PubMed  Google Scholar 

  66. Kelleher, T.B., Mehta, S.H., Bhaskar, R., Sulkowski, M., Astemborski, J., Thomas, D.L., et al. (2005) Prediction of hepatic fibro-sis in HIV/HCV co-infected patients using serum fibrosis markers: the SHASTA index. J. Hepatol. 43, 78–84

    Article  PubMed  Google Scholar 

  67. Nunes, D., Fleming, C., Offner, G., O'Brien, M., Tumilty, S., Fix, O., et al. (2005) HIV infection does not affect the performance of noninvasive markers of fibrosis for the diagnosis of hepatitis C virus-related liver disease. J. Acquir. Immune Defic. Syndr. 40, 538–544

    Article  PubMed  Google Scholar 

  68. Zheng, M., Cai, W.M., Zhao, J.K., Zhu, S.M., and Liu, R.H. (2005) Determination of serum levels of YKL-40 and hyaluronic acid in patients with hepatic fibrosis due to schisto-somiasis japonica and appraisal of their clinical value. Acta Trop. 96, 148–152

    Article  PubMed  Google Scholar 

  69. Kamal, S.M., Turner, B., He, Q., Rasenack, J., Bianchi, L., Al Tawil, A., et al. (2006) Progression of fibrosis in hepatitis C with and without schistosomiasis: correlation with serum markers of fibrosis. Hepatology 43, 771–779

    Article  CAS  PubMed  Google Scholar 

  70. Johansen, J.S., Cintin, C., Jørgensen, M., Kamby, C., and Price, P.A. 1995 Serum YKL-40: a new potential marker of prognosis and location of metastases of patients with recurrent breast cancer. Eur. J. Cancer 31A,1437–1442

    Article  CAS  PubMed  Google Scholar 

  71. Jensen, B.V., Johansen, J.S., and Price, P.A. (2003) High levels of serum HER-2/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer. Clin. Cancer Res. 9, 501–512

    Google Scholar 

  72. Johansen, J.S., Christensen, I.J., Riisbro, R., Greenall, M., Han, C., Price, P.A., et al. (2003) High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival. Breast Cancer Res. Treat. 80, 15–21

    Article  CAS  PubMed  Google Scholar 

  73. Cintin, C., Johansen, J.S., Christensen, I.J., Price, P.A., Sørensen, S., Nielsen, H.J. (1999) Serum YKL-40 and colorectal cancer. Br. J. Cancer 79, 1494–1499

    Article  CAS  PubMed  Google Scholar 

  74. Cintin, C., Johansen, J.S., Christensen, I.J., Price, P.A., Sørensen, S., Nielsen, H.J. (2002) High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. Cancer 95, 267–274

    Article  PubMed  Google Scholar 

  75. Høgdall, E.V.S., Johansen, J.S., Kjaer, S.K. Price, P.A., Christensen, L., Blaakjaer, J., et al. (2003) High plasma YKL-40 level in patients with ovarian cancer stage III is related to shorter survival. Oncol. Rep. 10, 1535–1538

    PubMed  Google Scholar 

  76. Dupont, J., Tanwar, M.K., Thaler, H.T., Fleisher, M., Kauff, N., Hensley, M.L., et al. (2004) Early detection and prognosis of ovarian cancer using serum YKL-40. J. Clin. Oncol. 22, 3330–3339

    Article  CAS  Google Scholar 

  77. Dehn, H., Høgdall, E.V.S., Johansen, J.S., Jørgensen, M., Price, P.A., Engelholm, S.A., et al. (2003) Plasma YKL-40, as a prognostic tumor marker in recurrent ovarian cancer. Acta. Obstet. Gynaecol. Scand. 82, 287–293

    Google Scholar 

  78. Johansen, J.S., Drivsholm, L., Price, P.A., and Christensen, I.J. (2004) High serum YKL-40 level in patients with small cell lung cancer is related to early death. Lung Cancer 46, 333–340

    Article  PubMed  Google Scholar 

  79. Brasso, K., Christensen, I.J., Johansen, J.S., Teisner, B., Garnero, P., Price, P.A., et al. (2006) Prognostic value of PINP, bone alkaline phosphatase, CTX-I and YKL-40 in patients with metastatic prostate carcinoma. Prostate 66, 503–513

    Article  CAS  PubMed  Google Scholar 

  80. Geertsen, P.F., Johansen, J.S., von der Maase, H., Jensen, B.V., and Price, P.A. (2003) High pretreatment serum level of YKL-40 is related to short survival in patients with advanced renal cell carcinoma treated with high-dose continuous intravenous infusion of inter-leukin-2. ASCO Ann. Meet. Proc. 22, 399 (Abstract 1603)

    Google Scholar 

  81. Diefenbach, C.S., Shah, Z., Iasonos, A., Bar-akat, R.R., Levine, D.A., Aghajanian, C., et al. (2007) Preoperative serum YKL-40 is a marker for detection and prognosis of endometrial cancer. Gynecol. Oncol. 104, 435–442

    Article  CAS  PubMed  Google Scholar 

  82. Johansen, J.S., Roslind, A., Palle, C., Chris-tensen, I.J., Nielsen, H.J., Price P.A., et al. (2006) Serum YKL-40 levels in patients with cervical cancer are elevated compared to patients with cervical intraepithelial neoplasia and healthy controls. ASCO Ann. Meet. Proc. 24, 267 (Abstract 5047)

    Google Scholar 

  83. Roslind, A., Johansen, J.S., Christensen, I.J., Kiss, K., Balslev, E., Nielsen, D.L., et al. (2008) High serum levels of YKL-40 in patients with squamous cell carcinoma of the head and neck are associated with short survival. Int. J. Cancer 122, 857–863

    Article  CAS  PubMed  Google Scholar 

  84. Hormigo, A., Gu, B., Karimi, S., Riedel, E., Panageas, K.S., Edgar, M.A., et al. (2006) YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas. Clin. Cancer Res. 12, 5698–5704

    Article  CAS  PubMed  Google Scholar 

  85. Schmidt, H., Johansen, J.S., Gehl, J., Geert-sen, P.F., Fode, K., and von der Maase, H. (2006) Elevated serum level of YKL-40 is an independent prognostic factor for poor survival in patients with metastatic melanoma. Cancer 106, 1130–1139

    Article  CAS  PubMed  Google Scholar 

  86. Schmidt, H., Johansen, J.S., Sjoegren, P. Christensen, I.J., Sørensen, B.S., Fode, K., et al. (2006) Serum YKL-40 predicts relapse-free and overall survival in patients with American Joint Committee on Cancer stage I and II melanoma. J. Clin. Oncol. 24, 798–804

    Article  CAS  PubMed  Google Scholar 

  87. Bergmann, O.J., Johansen, J.S., Klausen, T.W., Mylin, A.K., Kristensen, J.S., Kjeldsen, E., et al. (2005) High serum concentration of YKL-40 is associated with a short survival in patients with acute myeloid leukemia. Clin. Cancer Res. 11, 8644–8652

    Article  CAS  PubMed  Google Scholar 

  88. Mylin, A.K., Rasmussen, T., Johansen, J.S., Knudsen, L.M., Nørgaard, P.H., Lenhoff, S., et al. (2006) Serum YKL-40 concentrations in newly diagnosed multiple myeloma patients and YKL-40 expression in malignant plasma cells. Eur. J. Hematol. 77, 416–424

    Article  CAS  Google Scholar 

  89. Johansen, J.S., Jensen, B.V., Roslind, A., Nielsen, D., Price, P.A. (2006) Review. Serum YKL-40, a new prognostic biomarker in cancer patients? Cancer Epidemiol. Biomarkers Prev. 15, 194–202

    Article  CAS  PubMed  Google Scholar 

  90. Johansen, J.S., Jensen, B.V., Roslind, A., and Price, P.A., et al. (2007) Review. Is YKL-40 a new therapeutic target in cancer? Expert Opin. Ther. Targets 11, 219–234

    Article  CAS  PubMed  Google Scholar 

  91. Johansen, J.S., Brasso, K., Iversen, P., Teis-ner, B., Garnero, P., Price, P.A., et al. (2007) Changes of biochemical markers of bone turnover and YKL-40 following hormonal treatment for metastatic prostate cancer are related to survival. Clin. Cancer. Res. 13, 3244–3249

    Article  CAS  PubMed  Google Scholar 

  92. Høgdall, E.V.S., Johansen, J.S., Kjaer, S.K., Price, P.A., Blaakjaer, J., Høgdall, C.K. (2000) Stability of YKL-40 concentration in blood samples. Scand. J. Clin. Lab. Invest. 60, 247–252

    Article  PubMed  Google Scholar 

  93. Johansen, J.S., Lottenburger, T., Nielsen, H.J., Jensen, J.E.B., Svendsen, M.N., Kollerup, G., et al. (2008) Diurnal, weekly, and long time variation in serum concentrations of YKL-40 in healthy subjects. Cancer Epidemiol Prev. 17, 2603–2608

    Article  CAS  Google Scholar 

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Acknowledgments

The authors thank Professor Ph.D. Paul A. Price, Department of Biology, University of California, San Diego, California, USA for the kind donation of the monoclonal YKL-40 antibody. MD Eva Balslev, Department of Pathology, Herlev Hospital, University of Copenhagen, Denmark is thanked for assistance with development of the immunohistochemical and immunocyto-chemical methods. Technicians Hanife Dzaferi and Stine Jør-gensen, Department of Pathology, Herlev Hospital, University of Copenhagen, Denmark are thanked for technical assistance with the immunostainings. Molecular biologist, Ph.D. Nanna Junker, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen and technician Pia Knudsen, Institute of Molecular Pathology, University of Copenhagen are thanked for development of and for technical assistance with the in situ hybridization. Ph.D. Lars A. Larsen, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark is thanked for providing information regarding the PCR analysis. Keld B. Ottosen, The Panum Institute, is thanked for the final layout of the figures.

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Authors and Affiliations

  1. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark

    Anne Roslind

  2. Department of Rheumatology, Herlev Hospital, University of Copenhagen, Herlev, Denmark

    Julia S. Johansen

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  1. Anne Roslind
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  2. Julia S. Johansen
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Editors and Affiliations

  1. National Cancer Institute at Frederick, SAIC-Frederick, Inc., Frederick, MD, USA

    Serguei V. Kozlov

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Roslind, A., Johansen, J.S. (2009). YKL-40: A Novel Marker Shared by Chronic Inflammation and Oncogenic Transformation. In: Kozlov, S.V. (eds) Inflammation and Cancer. Methods in Molecular Biology™, vol 511. Humana Press. https://doi.org/10.1007/978-1-59745-447-6_7

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  • DOI: https://doi.org/10.1007/978-1-59745-447-6_7

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-14-5

  • Online ISBN: 978-1-59745-447-6

  • eBook Packages: Springer Protocols

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