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Open Access 01-08-2013 | Original Article

Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours

Authors: Agnieszka Szala, Sambor Sawicki, Anna St. Swierzko, Janusz Szemraj, Marcin Sniadecki, Mateusz Michalski, Andrzej Kaluzynski, Jolanta Lukasiewicz, Anna Maciejewska, Dariusz Wydra, David C. Kilpatrick, Misao Matsushita, Maciej Cedzynski

Published in: Cancer Immunology, Immunotherapy | Issue 8/2013

Abstract

Ficolins are serum pattern recognition molecules. They have opsonic properties and are able to activate complement via the lectin pathway. This paper reports investigations concerning ficolin-2 and ficolin-3 in ovarian cancer (OC). Their serum levels, single nucleotide polymorphisms of the corresponding FCN2 and FCN3 genes and specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary OC and 197 controls operated on for reasons other than malignancies. The latter consisted of two reference groups: those with benign tumours (n = 123) and those with normal ovaries (NO) (n = 74). Serum ficolin-2 and ficolin-3 concentrations were higher among patients with malignant disease when compared with either of the reference groups. A significant correlation between ficolin-2 and ficolin-3 concentrations was found, while no correlations with CA125 antigen or CRP were observed. No differences in the frequency of single nucleotide polymorphisms at sites −64, −4 (promoter), +6359, or +6424 (exon 8) (FCN2 gene) nor in the frame-shift mutation 1637delC (FCN3 gene) were found between investigated groups. In contrast to serum concentrations, the expression of FCN2 gene (reported for the first time in ovarian sections) was significantly lower in women with OC in comparison with patients with NO but not with benign ovarian tumours. In case of FCN3 gene, its expression levels in OC group inversely correlated with serum ficolin-3 and were lower in comparison with controls.

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Kilpatrick DC, Chalmers JD (2012) Human L-ficolin (ficolin-2) and its clinical significance. J Biomed Biotechnol 2012:138797PubMedCrossRef

Tsujimura M, Ishida C, Sagara Y, Miyazaki T, Murakami K, Shiraki H, Okochi K, Maeda Y (2001) Detection of serum thermolabile beta-2 macroglycoprotein (Hakata antigen) by enzyme-linked immunosorbent assay using polysaccharide produced by Aerococcus viridans. Clin Diagn Lab Immunol 8:454–459PubMed

Swierzko A, Lukasiewicz J, Cedzynski M, Maciejewska A, Jachymek W, Niedziela T, Matsushita M, Lugowski C (2012) New functional ligands for ficolin-3 among lipopolysaccharides of Hafnia alvei. Glycobiology 22:267–280PubMedCrossRef

Kuraya M, Ming Z, Liu X, Matsushita M, Fujita T (2005) Specific binding of L-ficolin and H-ficolin to apoptotic cells leads to complement activation. Immunobiology 209:689–697PubMedCrossRef

Honore C, Hummelshoj T, Hansen BE, Madsen HO, Eggleton P, Garred P (2007) The innate immune component ficolin 3 (Hakata antigen) mediates the clearance of late apoptotic cells. Arthritis Rheum 56:1598–1607PubMedCrossRef

Hummelshoj T, Munthe-Fog L, Madsen HO, Fujita T, Matsushita M, Garred P (2005) Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2. Hum Mol Genet 14:1651–1658PubMedCrossRef

Hummelshoj T, Munthe-Fog L, Madsen HO, Garred P (2008) Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns. Mol Immunol 45:2508–2520PubMedCrossRef

Herpers BL, Immink MM, de Jong BA, van Velzen-Blad H, de Jongh BM, van Hannen EJ (2006) Coding and non-coding polymorphisms in the lectin pathway activator L-ficolin gene in 188 Dutch blood bank donors. Mol Immunol 43:851–855PubMedCrossRef

Cedzynski M, Nuytinck L, Atkinson AP, St Swierzko A, Zeman K, Szemraj J, Szala A, Turner ML, Kilpatrick DC (2007) Extremes of L-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene. Clin Exp Immunol 150:99–104PubMedCrossRef

10.

Garred P, Honore C, Ma YJ, Rorvig S, Cowland J, Borregaard N, Hummelshoj T (2010) The genetics of ficolins. J Innate Immun 2:3–16PubMedCrossRef

11.

Munthe-Fog L, Hummelshoj T, Ma YJ, Hansen BE, Koch C, Madsen HO, Skjodt K, Garred P (2008) Characterization of a polymorphism in the coding sequence of FCN3 resulting in a ficolin-3 (Hakata antigen) deficiency state. Mol Immunol 45:2660–2666PubMedCrossRef

12.

Munthe-Fog L, Hummelshoj T, Honore C, Madsen HO, Permin H, Garred P (2009) Immunodeficiency associated with FCN3 mutation and ficolin-3 deficiency. N Engl J Med 360:2637–2644PubMedCrossRef

13.

Schlapbach LJ, Thiel S, Kessler U, Ammann RA, Aebi C, Jensenius JC (2011) Congenital H-ficolin deficiency in premature infants with severe necrotising enterocolitis. Gut 60:1438–1439PubMedCrossRef

14.

Michalski M, Szala A, Swierzko St A, Lukasiewicz J, Maciejewska A, Kilpatrick DC, Matsushita M, Domzalska-Popadiuk I, Borkowska-Klos M, Sokolowska A, Szczapa J, Lugowski C, Cedzynski M (2012) H-ficolin (ficolin-3) concentrations and FCN3 gene polymorphism in neonates. Immunobiology 217:730–737PubMedCrossRef

15.

Andersen JD, Boylan KL, Xue FS, Anderson LB, Witthuhn BA, Markowski TW, Higgins L, Skubitz AP (2010) Identification of candidate biomarkers in ovarian cancer serum by depletion of highly abundant proteins and differential in-gel electrophoresis. Electrophoresis 31:599–610PubMedCrossRef

16.

Hummelshoj T, Munthe Fog L, Madsen HO, Sim RB, Garred P (2008) Comparative study of the human ficolins reveals unique features of ficolin-3 (Hakata antigen). Mol Immunol 45:1623–1632PubMedCrossRef

17.

Kuraya M, Matsushita M, Endo Y, Thiel S, Fujita T (2003) Expression of H-ficolin/Hakata antigen, mannose-binding lectin-associated serine protease (MASP)-1 and MASP-3 by human glioma cell line T98G. Int Immunol 15:109–117PubMedCrossRef

18.

Swierzko AS, Florczak K, Cedzynski M, Szemraj J, Wydra D, Bak-Romaniszyn L, Emerich J, Sulowska Z (2007) Mannan-binding lectin (MBL) in women with tumours of the reproductive system. Cancer Immunol Immunother 56:959–971PubMedCrossRef

19.

Leth-Larsen R, Floridon C, Nielsen O, Holmskov U (2004) Surfactant protein D in the female genital tract. Mol Hum Reprod 10:149–154PubMedCrossRef

20.

Hansen S, Selman L, Palaniyar N, Ziegler K, Brandt J, Kliem A, Jonasson M, Skjoedt MO, Nielsen O, Hartshorn K, Jørgensen TJ, Skjødt K, Holmskov U (2010) Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity. J Immunol 185(6096):6104

21.

Kilpatrick DC, Fujita T, Matsushita M (1999) P35, an opsonic lectin of the ficolin family, in human blood from neonates, normal adults, and recurrent miscarriage patients. Immunol Lett 67:109–112PubMedCrossRef

22.

Szala A, Swierzko St A, Cedzynski M (2013) Cost-effective procedures for genotyping of human FCN2 gene single nucleotide polymorphisms. Immunogenetics 65:439–446PubMedCrossRef

23.

Li YL, Ye F, Hu Y, Lu WG, Xie X (2009) Identification of suitable reference genes for gene expression studies of human serous ovarian cancer by real-time polymerase chain reaction. Anal Biochem 394:110–116PubMedCrossRef

24.

Winer J, Jung CK, Shackel I, Williams PM (1999) Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Anal Biochem 270:41–49PubMedCrossRef

25.

Bertenshaw GP, Yip P, Seshaiah P, Zhao J, Chen T-H, Wiggins WS, Mapes JP, Mansfield BC (2008) Multianalyte profiling of serum antigens and autoimmune and infectious disease molecule to identify biomarkers dysregulated in epithelial ovarian cancer. Cancer Epidemiol Biomarkers 17:2872–2881CrossRef

26.

Ytting H, Jensenius JC, Christensen IJ, Thiel S, Nielsen HJ (2004) Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer. Scand J Gastroenterol 39:674–679PubMedCrossRef

27.

Ytting H, Christensen IJ, Thiel S, Jensenius JC, Nielsen HJ (2005) Serum mannan-binding lectin-associated serine protease 2 levels in colorectal cancer: relation to recurrence and mortality. Clin Cancer Res 11:1441–1446PubMedCrossRef

28.

Vazquez-Ortíz G, Ciudad CJ, Piña P, Vazquez K, Hidalgo A, Alatorre B, Garcia JA, Salamanca F, Peralta-Rodriguez R, Rangel A, Salcedo M (2005) Gene identification by cDNA arrays in HPV-positive cervical cancer. Arch Med Res 36:448–458PubMedCrossRef

29.

Arellano-Garcia ME, Li R, Liu X, Xie Y, Yan X, Lod JA, Hu S (2010) Indentification of tetranectin as a potential biomarker for metastatic oral cancer. Int J Mol Sci 11:3106–3121PubMedCrossRef

30.

Kilpatrick DC, McLintock LA, Allan EK, Copland M, Fujita T, Jordanides NE, Koch C, Matsushita M, Shiraki H, Stewart K, Tsujimura M, Turner ML, Franklin IM (2003) No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections. Clin Exp Immunol 134:279–284PubMedCrossRef

31.

Ameye L, Paesmans M, Thiel S, Jensenius JC, Aoun M (2012) M-ficolin levels are associated with the occurrence of severe infections in patients with haematological cancer undergoing chemotherapy. Clin Exp Immunol 167:303–308PubMedCrossRef

32.

Luo JH, Ren B, Keryanov S, Tseng GC, Rao UN, Monga SP, Strom S, Demetris AJ, Nalesnik M, Yu YP, Ranganathan S, Michalopoulos GK (2006) Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology 44:1012–1024PubMedCrossRef

33.

Shi I, Hashemi Sadraei N, Duan ZH, Shi T (2011) Aberrant signaling pathways in squamous cell lung carcinoma. Cancer Inform 10:273–285PubMedCrossRef

34.

Schlapbach LJ, Aebi C, Hansen AG, Hirt A, Jensenius JC, Ammann RA (2009) H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients. Clin Exp Immunol 157:83–89PubMedCrossRef

35.

Hefler-Frischmuth K, Hefler LA, Heinze G, Paseka V, Grimm C, Tempfer CB (2009) Serum C-reactive protein in the differential diagnosis of ovarian masses. Eur J Obstet, Gynecol Reprod Biol 147:65–68CrossRef

36.

Andersen T, Munthe-Fog L, Garred P, Jacobsen S (2009) Serum levels of ficolin-3 (Hakata antigen) in patients with systemic lupus erythematosus. J Rheumatol 36:757–759PubMedCrossRef

37.

Liu J, Ali MA, Shi Y, Zhao Y, Luo F, Yu J, Xiang T, Tang J, Li D, Hu Q, Ho W, Zhang X (2009) Specifically binding of L-ficolin to N-glycans of HCV envelope glycoproteins E1 and E2 leads to complement activation. Cell Mol Immunol 4:235–244CrossRef

38.

Hoang TV, Toan NL, le Song H, Ouf EA, Bock CT, Kremsner PG, Kun JF, Velavan TP (2011) Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients. PLoS ONE 6:e28113PubMedCrossRef

39.

Roy S, Biswas S, Saroha A, Sahu D, Das HR (2012) Enhanced expression and fucosylation of ficolin3 in plasma of RA patients. Clin Biochem 46:160–163PubMedCrossRef

40.

Sallenbach S, Thiel S, Aebi C, Otth M, Bigler S, Jensenius JC, Schlapbach LJ, Ammann RA (2011) Serum concentrations of lectin-pathway components in healthy neonates, children and adults: mannan-binding lectin (MBL), M-, L-, and H-ficolin, and MBL-associated serine protease-2 (MASP-2). Pediatr Allergy Immunol 22:424–430PubMedCrossRef

41.

Ma YG, Cho MY, Zhao M, Park JW, Matsushita M, Fujita T, Lee BL (2004) Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement. J Biol Chem 279:25307–25312PubMedCrossRef

42.

Vetvicka V (2011) Glucan—immunostimulant, adjuvant, potential drug. World J Clin Oncol 2:115–119PubMedCrossRef

Title: Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours
Authors: Agnieszka Szala
Sambor Sawicki
Anna St. Swierzko
Janusz Szemraj
Marcin Sniadecki
Mateusz Michalski
Andrzej Kaluzynski
Jolanta Lukasiewicz
Anna Maciejewska
Dariusz Wydra
David C. Kilpatrick
Misao Matsushita
Maciej Cedzynski
Publication date: 01-08-2013
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 8/2013
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-013-1445-3

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