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Tumor Biology
Published in: Tumor Biology 7/2016

01-07-2016 | Original Article

YKL-40/chitinase-3-like protein 1 is associated with poor prognosis and promotes cell growth and migration of cholangiocarcinoma

Authors: Sunisa Thongsom, Wethaka Chaocharoen, Atit Silsirivanit, Sopit Wongkham, Banchob Sripa, Han Choe, Wipa Suginta, Chutima Talabnin

Published in: Tumor Biology | Issue 7/2016

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Abstract

YKL-40, a chitinase-like glycoprotein, is expressed at a high level in cancer patients. Its exact function is unknown and is the subject of current investigation. Here, we report the correlation of plasma YKL-40 levels with clinicopathological features of cholangiocarcinoma (CCA), a lethal bile duct cancer, particularly prevalent in Northeastern Thailand. Statistical analysis of plasma YKL-40 concentrations in 57 CCA patients and 41 normal healthy subjects gave a median value of 169.5 ng/mL for CCA patients compared with 46.9 ng/mL for the control subjects (P < 0.0001). There was no significant association of plasma YKL-40 levels with patient age, tumor grade, or histology type. However, Kaplan-Meier analysis suggested that the elevated plasma YKL-40 level was particularly associated with short survival in CCA patients (P = 0.038). Immunohistochemical examination of 34 CCA tissues revealed low expression of YKL-40 in CCA cells, but high expression in adjacent intratumoral stroma, liver, and connective tissues. Univariate analysis showed significant association of the intratumoral YKL-40 expression in CCA tissues with the non-papillary type CCA. Addition of rYKL-40 in the culture medium and transient expression of YKL-40 in CCA cell lines were shown to promote the growth and migration of the tumor cells, and that YKL-40 interacted with a cell-surface receptor involved in the Akt/Erk-mediated pathway. In conclusion, our results support the proposal of YKL-40 as a new candidate prognostic biomarker for cancer diseases.
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Literature
1.
Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC. Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol. 2002;37:806–13.CrossRefPubMed
2.
Sirica AE. Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy. Hepatology. 2005;41:5–15.CrossRefPubMed
3.
Taylor-Robinson SD, Toledano MB, Arora S, Keegan TJ, Hargreaves S, Beck A, et al. Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968–1998. Gut. 2001;48:816–20.CrossRefPubMedPubMedCentral
4.
Shin HR, Oh JK, Masuyer E, Curado MP, Bouvard V, Fang Y, et al. Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma—focus on East and South-Eastern Asia. Asian Pac J Cancer P. 2010;11:1159–66.
5.
Bragazzi MC, Cardinale V, Carpino G, Venere R, Semeraro R, Gentile R, et al. Cholangiocarcinoma: epidemiology and risk factors. Transl Gastrointest Cancer. 2011;1:21–32.
6.
Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004;99:523–6.CrossRefPubMed
7.
Sripa B, Pairojkul C. Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroen. 2008;24:349–56.CrossRef
8.
Srivatanakul P, Ohshima H, Khlat M, Parkin M, Sukarayodhin S, Brouet I, et al. Endogenous nitrosamines and liver fluke as risk factors for cholangiocarcinoma in Thailand. IARC Sci Publ. 1991;105:88–95.
9.
Silsirivanit A, Proungvitaya S, Sawanyawisuth K, Wongkham C, Wongkham S. Biomarkers in bile duct cancers: current status. Srinagarind Med J. 2012;27:405–12.
10.
Wongkham S, Silsirivanit A. State of serum markers for detection of cholangiocarcinoma. Asian Pac J Cancer P. 2012;13:17–27.
11.
Hakala BE, White C, Recklies AD. 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. 1993;268:25803–10.PubMed
12.
Johansen JS, Kirwan JR, Price PA, Sharif M. Serum YKL-40 concentrations in patients with early rheumatoid arthritis: relation to joint destruction. Scand J Rheumatol. 2001;30:297–304.CrossRefPubMed
13.
Nordenbaek C, Johansen JS, Junker P, Borregaard N, Sørensen O, Price PA. YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization. J Infect Dis. 1999;180:1722–6.CrossRefPubMed
14.
Fusetti F, Pijning T, Kalk KH, Bos E, Dijkstra BW. Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39. J Biol Chem. 2003;278:37753–60.CrossRefPubMed
15.
Renkema GH, Boot RG, Au FL, Donker-Koopman WE, Strijland A, Muijsers AO, et al. 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 Chem. 1998;251:504–9.CrossRef
16.
Olland AM, Strand J, Presman E, Czerwinski R, Joseph-McCarthy D, Krykbaev R, et al. Triad of polar residues implicated in pH specificity of acidic mammalian chitinase. Protein Sci. 2009;18:569–78.PubMedPubMedCentral
17.
Perrakis A, Tews I, Dauter Z, Oppenheim AB, Chet I, Wilson KS, et al. Crystal structure of a bacterial chitinase at 2.3 A resolution. Structure. 1994;2:1169–80.CrossRefPubMed
18.
Ranok A, Wongsantichon J, Robinson RC, Suginta W. Structural and thermodynamic insights into chitooligosaccharide binding to human cartilage chitinase 3-like protein 2 (CHI3L2 or YKL-39). J Biol Chem. 2015;290:2617–29.CrossRefPubMed
19.
Songsiriritthigul C, Pantoom S, Aguda AH, Robinson RC, Suginta W. Crystal structures of Vibrio harveyi chitinase A complexed with chitooligosaccharides: implications for the catalytic mechanism. J Struct Biol. 2008;162:491–9.CrossRefPubMed
20.
Houston DR, Recklies AD, Krupa JC, van Aalten DM. Structure and ligand-induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes. J Biol Chem. 2003;278:30206–12.CrossRefPubMed
21.
Francescone RA, Scully S, Faibish M, Taylor SL, Oh D, Moral L, et al. Role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma. J Biol Chem. 2011;286:15332–43.CrossRefPubMedPubMedCentral
22.
Junker N, Johansen JS, Andersen CB, Kristjansen PE. Expression of YKL-40 by peritumoral macrophages in human small cell lung cancer. Lung Cancer. 2005;48:223–31.CrossRefPubMed
23.
Shao R, Hamel K, Petersen L, Cao QJ, Arenas RB, Bigelow C, et al. YKL-40, a secreted glycoprotein, promotes tumor angiogenesis. Oncogene. 2009;28:4456–68.CrossRefPubMedPubMedCentral
24.
Kawada M, Seno H, Kanda K, Nakanishi Y, Akitake R, Komekado H, et al. Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer. Oncogene. 2012;31:3111–23.CrossRefPubMed
25.
Ku BM, Lee YK, Ryu J, Jeong JY, Choi J, Eun KM, et al. CHI3L1 (YKL-40) is expressed in human gliomas and regulates the invasion, growth and survival of glioma cells. Int J Cancer. 2011;128:1316–26.CrossRefPubMed
26.
Kucur M, Isman FK, Balci C, Onal B, Hacibekiroglu M, Ozkan F, et al. Serum YKL-40 levels and chitotriosidase activity as potential biomarkers in primary prostate cancer and benign prostatic hyperplasia. Urol Oncol. 2008;26:47–52.CrossRefPubMed
27.
Thom I, Andritzky B, Schuch G, Burkholder I, Edler L, Johansen JS, et al. Elevated pretreatment serum concentration of YKL-40—an independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer. Cancer. 2010;116:4114–21.CrossRefPubMed
28.
Wang D, Zhai B, Hu F, Liu C, Zhao J, Xu J. High YKL-40 serum concentration is correlated with prognosis of Chinese patients with breast cancer. PLoS One. 2012;7:e51127.CrossRefPubMedPubMedCentral
29.
Xiao XQ, Hassanein T, Li QF, Liu W, Zheng YH, Chen J. YKL-40 expression in human hepatocellular carcinoma: a potential biomarker? Hepatob Pancreat Dis. 2011;10:605–10.CrossRef
30.
Yamac D, Ozturk B, Coskun U, Tekin E, Sancak B, Yildiz R, et al. Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer. Adv Ther. 2008;25:801–9.CrossRefPubMed
31.
Johansen JS, Jensen BV, Roslind A, Nielsen D, Price PA. Serum YKL-40, a new prognostic biomarker in cancer patients? Cancer Epidem Biomar. 2006;15:194–202.CrossRef
32.
33.
Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRefPubMed
34.
Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.CrossRefPubMed
35.
Utispan K, Thuwajit P, Abiko Y, Charngkaew K, Paupairoj A, Chau-in S, et al. Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker. Mol Cancer. 2010;9:1–20.CrossRef
36.
Cintin C, Johansen JS, Christensen IJ, Price PA, Sorensen S, Nielsen HJ. High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. Cancer. 2002;95:267–74.CrossRefPubMed
37.
Hogdall E, Johansen J, Kjaer S, Price P, Christensen L, Blaakaer J, et al. High plasma YKL-40 level in patients with ovarian cancer stage III is related to shorter survival. Oncol Rep. 2003;10:1535–8.PubMed
38.
Johansen JS, Christensen IJ, Riisbro R, Greenall M, Han C, Price PA, et al. High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival. Breast Cancer Res Treat. 2003;80:15–21.CrossRefPubMed
39.
Dehn H, Hogdall E, Johansen J, Jorgensen M, Price P, Engelholm S, et al. Plasma YKL-40, as a prognostic tumor marker in recurrent ovarian cancer. Acta Obstet Gynecol Scand. 2003;82:287–93.CrossRefPubMed
40.
Jensen BV, Johansen JS, Price PA. High levels of serum HER-2/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer. Clin Cancer Res. 2003;9:4423–34.PubMed
41.
Tarpgaard LS, Guren TK, Glimelius B, Christensen IJ, Pfeiffer P, Kure EH, et al. Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab: RESULTS from the NORDIC VII Study. PLoS One. 2014;9:e87746.CrossRefPubMedPubMedCentral
42.
Zhu CB, Chen LL, Tian JJ, Su L, Wang C, Gai ZT, et al. Elevated serum YKL-40 level predicts poor prognosis in hepatocellular carcinoma after surgery. Ann Surg Oncol. 2012;19:817–25.CrossRefPubMed
43.
Fan JT, Li MJ, Shen P, Xu H, Li DH, Yan HQ. Serum and tissue level of YKL-40 in endometrial cancer. Eur J Gynaecol Oncol. 2014;35:304–8.PubMed
44.
Bernardi D, Padoan A, Ballin A, Sartori M, Manara R, Scienza R, et al. Serum YKL-40 following resection for cerebral glioblastoma. J Neuro-Oncol. 2012;107:299–5.CrossRef
45.
Hogdall E, Ringsholt M, Hogdall C, Christensen IJ, Johansen J, Kjaer S, et al. YKL-40 tissue expression and plasma levels in patients with ovarian cancer. BMC Cancer. 2009;9:8.CrossRefPubMedPubMedCentral
46.
Brasso K, Christensen IJ, Johansen JS, Teisner B, Garnero P, Price PA, et al. Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006;66:503–13.CrossRefPubMed
47.
Ringsholt M, Hogdall EV, Johansen JS, Price PA, Christensen LH. YKL-40 protein expression in normal adult human tissues—an immunohistochemical study. J Mol Histol. 2007;38:33–43.CrossRefPubMed
48.
De Ceuninck F, Gaufillier S, Bonnaud A, Sabatini M, Lesur C, Pastoureau P. YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes. Biochem Bioph Res Co. 2001;285:926–31.CrossRef
49.
Recklies AD, White C, Ling H. The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. Biochem J. 2002;365:119–26.CrossRefPubMedPubMedCentral
50.
Ngernyuang N, Francescone RA, Jearanaikoon P, Daduang J, Supoken A, Yan W, et al. Chitinase 3 like 1 is associated with tumor angiogenesis in cervical cancer. Int J Biochem Cell B. 2014;51:45–52.CrossRef
51.
Nishikawa KC, Millis AJ. gp38k (CHI3L1) is a novel adhesion and migration factor for vascular cells. Exp Cell Res. 2003;287:79–87.CrossRefPubMed
52.
Singh SK, Bhardwaj R, Wilczynska KM, Dumur CI, Kordula T. A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40. J Biol Chem. 2011;286:39893–903.CrossRefPubMedPubMedCentral
53.
Harada K, Masuda S, Hirano M, Nakanuma Y. Reduced expression of syndecan-1 correlates with histologic dedifferentiation, lymph node metastasis, and poor prognosis in intrahepatic cholangiocarcinoma. Hum Pathol. 2003;34:857–63.CrossRefPubMed
54.
Utispan K, Sonongbua J, Thuwajit P, Chau-In S, Pairojkul C, Wongkham S, et al. Periostin activates integrin alpha5beta1 through a PI3K/AKTdependent pathway in invasion of cholangiocarcinoma. Int J Oncol. 2012;41:1110–8.PubMed
55.
Chaocharoen W, Suginta W, Limbut W, Ranok A, Numnuam A, Khunkaewla P, et al. Electrochemical detection of the disease marker human chitinase-3-like protein 1 by matching antibody-modified gold electrodes as label-free immunosensors. Bioelectrochemistry. 2015;101:106–13.CrossRefPubMed
Metadata
Title
YKL-40/chitinase-3-like protein 1 is associated with poor prognosis and promotes cell growth and migration of cholangiocarcinoma
Authors
Sunisa Thongsom
Wethaka Chaocharoen
Atit Silsirivanit
Sopit Wongkham
Banchob Sripa
Han Choe
Wipa Suginta
Chutima Talabnin
Publication date
01-07-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 7/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-4838-z

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