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01.03.2014 | Research Article

Milk fat globule epidermal growth factor 8 serves a novel biomarker of opisthorchiasis-associated cholangiocarcinoma

verfasst von: Zhiliang Wu, Thidarut Boonmars, Isao Nagano, Watcharin Loilome, Puangrat Yongvanit, Narong Khuntikeo, Phuangphaka Sadee Nielsen, Chawalit Paorojkul, Yuzo Takahashi, Yoichi Maekawa

Erschienen in: Tumor Biology | Ausgabe 3/2014

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Abstract

Milk fat globule epidermal growth factor 8 (MFG-E8) is a pleiotropic secreted glycoprotein to play roles in mediating immune tolerance and homeostasis maintenance and enhancing angiogenesis. To evaluate its value as a biomarker in opisthorchiasis-associated cholangiocarcinoma (CCA), the present study investigated MFG-E8 expression kinetics during the tumorigenesis in Opisthorchis viverrini infection-induced CCA, and demonstrated its expression in the tumor tissues of CCA patients and its serum level among them. During the tumorigenesis of CCA, MFG-E8 expression was increased in a time-dependent manner with the pathological processes. Absolutely higher expression of MFG-E8 messenger RNA was detected in the tumor tissues from CCA patients, compared with those in adjacent tissues. Immunobiochemical analysis showed that more than 90 % CCA cases were positive and the positive reaction located in the membrane and cytoplasm of the tumor cells. Moreover, the average serum level in the CCA patients was significantly higher than that in healthy individuals and those with O. viverrini infection or other parasitosis. Correlation analysis of MFG-E8 expression with CCA clinicopathology revealed that a high expression of MFG-E8 protein was significantly bound with a poor differentiation, pathological advanced stage, and metastasis of CCA. The multivariation analysis indicated that MFG-E8 was an independent prognostic factor. In addition, short hairpin RNA-mediated MFG-E8 knockdown in CCA cell line obviously suppressed the cell proliferation. Our results strongly suggested that MFG-E8 is a promising biomarker for the diagnosis, prognosis, and therapy target of opisthorchiasis-associated CCA.

Sithithaworn P, Andrews RH, Nguyen VD, Wongsaroj T, Sinuon M, Odermatt P, et al. The current status of opisthorchiasis and clonorchiasis in the Mekong Basin. Parasitol Int. 2012;61:10–6.PubMedCentralPubMedCrossRef

Thamavit W, Kongkanuntn R, Tiwawech D, Moore MA. Level of Opisthorchis infestation and carcinogen dose-dependence of cholangiocarcinoma induction in Syrian golden hamsters. Virchows Arch B Cell Pathol Inc Mol Pathol. 1987;54:52–8.CrossRef

Vatanasapt V, Uttaravichien T, Mairiang EO, Pairojkul C, Chartbanchachai W, Haswell-Elkins M. Cholangiocarcinoma in north-east Thailand. Lancet. 1990;335:116–7.PubMedCrossRef

Srivatanakul P, Ohshima H, Khlat M, Parkin M, Sukaryodhin S, Brouet I, et al. Opisthorchis viverrini infestation and endogenous nitrosamines as risk factors for cholangiocarcinoma in Thailand. Int J Cancer. 1991;48:821–5.PubMedCrossRef

Thamavit W, Pairojkul C, Tiwawech D, Itoh M, Shirai T, Ito N. Promotion of cholangiocarcinogenesis in the hamster liver by bile duct ligation after dimethylnitrosamine initiation. Carcinogenesis. 1993;14:2415–7.PubMedCrossRef

Shin HR, Oh JK, Masuyer E, Curado MP, Bouvard V, Fang YY, et al. Epidemiology of cholangiocarcinoma: an update focusing on risk factors. Cancer Sci. 2010;101:579–85.PubMedCrossRef

Sripa B, Bethony JM, Sithithaworn P, Kaewkes S, Mairiang E, Loukas A, et al. Opisthorchiasis and Opisthorchis-associated cholangiocarcinoma in Thailand and Laos. Acta Trop. 2011;120 Suppl 1:S158–168.PubMedCentralPubMedCrossRef

Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E, et al. The tumorigenic liver fluke Opisthorchis viverrini-multiple pathways to cancer. Trends Parasitol. 2012;28:395–407.PubMedCentralPubMedCrossRef

Ustundag Y, Bayraktar Y. Cholangiocarcinoma: a compact review of the literature. World J Gastroenterol. 2008;14:6458–2466.PubMedCentralPubMedCrossRef

10.

Mosconi S, Beretta GD, Labianca R, Zampino MG, Gatta G, Heinemann V. Cholangiocarcinoma. Crit Rev Oncol Hematol. 2009;69:259–70.PubMedCrossRef

11.

Tyson GL, El-Serag HB. Risk factors for cholangiocarcinoma. Hepatology. 2011;54:173–84.PubMedCentralPubMedCrossRef

12.

Gores GJ. Early detection and treatment of cholangiocarcinoma. Liver Transpl. 2000;6:s30–4.PubMedCrossRef

13.

Ni XG, Bai XF, Mao YL, Shao YF, Wu JX, Shan Y, et al. The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer. Eur J Surg Oncol. 2005;31:164–9.PubMedCrossRef

14.

Boonjaraspinyo S, Wu Z, Boonmars T, Kaewkes S, Loilome W, Sithithaworn P, et al. Overexpression of PDGFA and its receptor during carcinogenesis of Opisthorchis viverrini-associated cholangiocarcinoma. Parasitol Int. 2012;61:145–50.PubMedCrossRef

15.

Boonjaraspinyo S, Boonmars T, Wu Z, Loilome W, Sithithaworn P, Nagano I, et al. Platelet-derived growth factor may be a potential diagnostic and prognostic marker for cholangiocarcinoma. Tumour Biol. 2012;33:1785–802.PubMedCrossRef

16.

Wu Z, Boonmars T, Nagano I, Boonjaraspinyo S, Pinlaor S, Pairojkul C, et al. Alteration of galectin-1 during tumorigenesis of Opisthorchis viverrini infection-induced cholangiocarcinoma and its correlation with clinicopathology. Tumour Biol. 2012;33:1169–78.PubMedCrossRef

17.

Techasen A, Loilome W, Namwat N, Duenngai K, Cha'on U, Thanan R, et al. Opisthorchis viverrini-antigen induces expression of MARCKS during inflammation-associated cholangiocarcinogenesis. Parasitol Int. 2012;61:140–4.PubMedCrossRef

18.

Loilome W, Wechagama P, Namwat N, Jusakul A, Sripa B, Miwa M, et al. Expression of oxysterol binding protein isoforms in opisthorchiasis-associated cholangiocarcinoma: a potential molecular marker for tumor metastasis. Parasitol Int. 2012;61:136–9.PubMedCrossRef

19.

Yonglitthipagon P, Pairojkul C, Chamgramol Y, Mulvenna J, Sripa B (2010) Up-regulation of annexin A2 in cholangiocarcinoma caused by Opisthorchis viverrini and its implication as a prognostic marker. Int J Parasitol 40:1203–1212

20.

Sripa B, Thinkhamrop B, Mairiang E, Laha T, Kaewkes S, Sithithaworn P, et al. Elevated plasma IL-6 associates with increased risk of advanced fibrosis and cholangiocarcinoma in individuals infected by Opisthorchis viverrini. PLoS Negl Trop Dis. 2012;6:e1654.PubMedCentralPubMedCrossRef

21.

Wu Z, Boonmars T, Boonjaraspinyo S, Nagano I, Pinlaor S, Puapairoj A, et al. Candidate genes involving in tumorigenesis of cholangiocarcinoma induced by Opisthorchis viverrini infection. Parasitol Res. 2011;109:657–73.PubMedCrossRef

22.

Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S. Identification of a factor that links apoptotic cells to phagocytes. Nature. 2002;417:182–7.PubMedCrossRef

23.

Hanayama R, Tanaka M, Miyasaka K, Aozasa K, Koike M, Uchiyama Y, et al. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science. 2004;304:1147–50.PubMedCrossRef

24.

Atabai K, Fernandez R, Huang X, Ueki I, Kline A, Li Y, et al. Mfge8 is critical for mammary gland remodeling during involution. Mol Biol Cell. 2005;16:5528–37.PubMedCentralPubMedCrossRef

25.

Silvestre JS, Théry C, Hamard G, Boddaert J, Aguilar B, Delcayre A, et al. Lactadherin promotes VEGFdependent neovascularization. Nat Med. 2005;11:499–506.PubMedCrossRef

26.

Ensslin MA, Shur BD. Identification of mouse sperm SED1, a bimotif EGF repeat and discoidin-domain protein involved in sperm-egg binding. Cell. 2003;114:405–17.PubMedCrossRef

27.

Bu HF, Zuo XL, Wang X, Ensslin MA, Koti V, Hsueh W, et al. Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium. J Clin Invest. 2007;117:3673–83.PubMedCentralPubMed

28.

Larocca D, Peterson JA, Urrea R, Kuniyoshi J, Bistrain AM, Ceriani RL. A Mr 46 000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains. Cancer Res. 1991;51:4994–8.PubMed

29.

Yang C, Hayashida T, Forster N, Li C, Shen D, Maheswaran S, et al. The integrin alpha(v)beta(3–5) ligand MFG-E8 is a p63/p73 target gene in triple-negative breast cancers but exhibits suppressive functions in ER(+) and erbB2(+) breast cancers. Cancer Res. 2011;71:937–45.PubMedCentralPubMedCrossRef

30.

Oba J, Moroi Y, Nakahara T, Abe T, Hagihara A, Furue M. Expression of milk fat globule epidermal growth factor-VIII may be an indicator of poor prognosis in malignant melanoma. Br J Dermatol. 2011;165:506–12.PubMedCrossRef

31.

Sugano G, Bernard-Pierrot I, Laé M, Battail C, Allory Y, Stransky N, et al. Milk fat globule–epidermal growth factor–factor VIII (MFGE8)/lactadherin promotes bladder tumor development. Oncogene. 2011;30:642–53.PubMedCrossRef

32.

Neutzner M, Lopez T, Feng X, Bergmann-Leitner ES, Leitner WW, Udey MC. MFG-E8/lactadherin promotes tumor growth in an angiogenesis-dependent transgenic mouse model of multistage carcinogenesis. Cancer Res. 2007;67:6777–85.PubMedCrossRef

33.

Jinushi M, Nakazaki Y, Carrasco DR, Draganov D, Souders N, Johnson M, et al. Milk fat globule EGF-8 promotes melanoma progression through coordinated Akt and twist signaling in the tumor microenvironment. Cancer Res. 2008;68:8889–98.PubMedCrossRef

34.

Couto JR, Taylor MR, Godwin SG, Ceriani RL, Peterson JA. Cloning and sequence analysis of human breast epithelial antigen BA46 reveals an RGD cell adhesion sequence presented on an epidermal growth factor-like domain. DNA Cell Biol. 1996;15:281–6.PubMedCrossRef

35.

Wang M, Fu Z, Wu J, Zhang J, Jiang L, Khazan B, et al. MFG-E8 activates proliferation of vascular smooth muscle cells via integrin signaling. Aging Cell. 2012;11:500–8.PubMedCentralPubMedCrossRef

36.

Boonmars T, Wu Z, Boonjaruspinyo S, Pinlaor S, Nagano I, Takahashi Y, et al. Alterations of gene expression of RB pathway in Opisthorchis viverrini infection-induced cholangiocarcinoma. Parasitol Res. 2009;105:1273–81.PubMedCrossRef

37.

Boonmars T, Wu Z, Boonjaraspinyo S, Puapairoj A, Kaewsamut B, Nagano I, et al. Involvement of c-Ski oncoprotein in carcinogenesis of cholangiocacinoma induced by Opisthorchis viverrini and N-nitrosodimethylamine. Pathol Oncol Res. 2011;17:219–27.PubMedCrossRef

38.

Watanabe T, Totsuka R, Miyatani S, Kurata S, Sato S, Katoh I, et al. Production of the long and short forms of MFG-E8 by epidermal keratinocytes. Cell Tissue Res. 2005;321:185–93.PubMedCrossRef

39.

Ensslin MA, Shur BD. The EGF repeat and discoidin domain protein, SED1/MFG-E8, is required for mammary gland branching morphogenesis. Proc Natl Acad Sci U S A. 2007;104:2715–20.PubMedCentralPubMedCrossRef

40.

Giuffrida MG, Cavaletto M, Giunta C, Conti A, Godovac-Zimmermann J. Isolation and characterization of full and truncated forms of human breast carcinoma protein BA46 from human milk fat globule membranes. J Protein Chem. 1998;17:143–8.PubMedCrossRef

41.

Carrascosa C, Obula RG, Missiaglia E, Lehr HA, Delorenzi M, Frattini M, et al. MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells. Oncogene. 2012;31:1521–32.PubMedCrossRef

42.

Nakatani H, Yasueda T, Oshima K, Nadano D, Matsuda T. Re-evaluation of milk-fat globule EGF-factor VIII (MFG-E8) as an intrinsic component of the mouse milk-fat globule membrane. Biosci Biotechnol Biochem. 2012;76:2055–60.PubMedCrossRef

43.

Newburg DS, Peterson JA, Ruiz-Palacios GM, Matson DO, Morrow AL, Shults J, et al. Role of human-milk lactadherin in protection against symptomatic rotavirus infection. Lancet. 1998;351:1160–4.PubMedCrossRef

Titel: Milk fat globule epidermal growth factor 8 serves a novel biomarker of opisthorchiasis-associated cholangiocarcinoma
verfasst von: Zhiliang Wu
Thidarut Boonmars
Isao Nagano
Watcharin Loilome
Puangrat Yongvanit
Narong Khuntikeo
Phuangphaka Sadee Nielsen
Chawalit Paorojkul
Yuzo Takahashi
Yoichi Maekawa
Publikationsdatum: 01.03.2014
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 3/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-013-1264-3

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