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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 10/2011

01-10-2011 | Original article

Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients

Authors: Fabio Morandi, Maria Valeria Corrias, Isabella Levreri, Paola Scaruffi, Lizzia Raffaghello, Barbara Carlini, Paola Bocca, Ignazia Prigione, Sara Stigliani, Loredana Amoroso, Soldano Ferrone, Vito Pistoia

Published in: Cancer Immunology, Immunotherapy | Issue 10/2011

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Abstract

The high molecular weight melanoma-associated antigen (HMW-MAA) and the cytoplasmic melanoma-associated antigen (cyt-MAA/LGALS3BP) are expressed in melanoma. Their serum levels are increased in melanoma patients and correlate with clinical outcome. We investigated whether these molecules can serve as prognostic markers for neuroblastoma (NB) patients. Expression of cyt-MAA and HMW-MAA was evaluated by flow cytometry in NB cell lines, patients’ neuroblasts (FI-NB), and short-term cultures of these latter cells (cNB). LGALS3BP gene expression was evaluated by RT–qPCR on FI-NB, cNB, and primary tumor specimens. Soluble HMW-MAA and cyt-MAA were tested by ELISA. Cyt-MAA and HMW-MAA were expressed in NB cell lines, cNB, and FI-NB samples. LGALS3BP gene expression was higher in primary tumors and cNB than in FI-NB samples. Soluble cyt-MAA, but not HMW-MAA, was detected in NB cell lines and cNBs supernatants. NB patients’ serum levels of both antigens were higher than those of the healthy children. High cyt-MAA serum levels at diagnosis associated with higher incidence of relapse, independently from other known risk factors. In conclusion, both HMW-MAA and cyt-MAA antigens, and LGALS3BP gene, were expressed by NB cell lines and patients’ neuroblasts, and both antigens’ serum levels were increased in NB patients. Elevated serum levels of cyt-MAA at diagnosis correlated with relapse, supporting that cyt-MAA may serve as early serological biomarker to individuate patients at higher risk of relapse that may require a more careful follow-up, after being validated in a larger cohort of patients at different time-points during follow-up. Given its immunogenicity, cyt-MAA may also be a potential target for NB immunotherapy.
Literature
1.
Labdenne P, Heikinheimo M (2002) Clinical use of tumor markers in childhood malignancies. Ann Med 34(5):316–323PubMedCrossRef
2.
Giacomini P, Gambari R, Barbieri R, Nistico P, Tecce R, Pestka S, Gustafsson K, Natali PG, Fisher PB (1986) Regulation of the antigenic phenotype of human melanoma cells by recombinant interferons. Anticancer Res 6(5):877–884PubMed
3.
Giacomini P, Veglia F, Cordiali Fei P, Rehle T, Natali PG, Ferrone S (1984) Level of a membrane-bound high-molecular-weight melanoma-associated antigen and a cytoplasmic melanoma-associated antigen in surgically removed tissues and in sera from patients with melanoma. Cancer Res 44(3):1281–1287PubMed
4.
Giacomini P, Viora M, Tecce R, Knowles DM, Natali PG, Ferrone S (1987) A cytoplasmic human melanoma associated antigen as a marker of activation in lymphoid cells. Cancer Res 47(19):5175–5180PubMed
5.
Goto Y, Ferrone S, Arigami T, Kitago M, Tanemura A, Sunami E, Nguyen SL, Turner RR, Morton DL, Hoon DS (2008) Human high molecular weight-melanoma-associated antigen: utility for detection of metastatic melanoma in sentinel lymph nodes. Clin Cancer Res 14(11):3401–3407PubMedCrossRef
6.
Luo W, Hsu JC, Tsao CY, Ko E, Wang X, Ferrone S (2005) Differential immunogenicity of two peptides isolated by high molecular weight-melanoma-associated antigen-specific monoclonal antibodies with different affinities. J Immunol 174(11):7104–7110PubMed
7.
Luo W, Ko E, Hsu JC, Wang X, Ferrone S (2006) Targeting melanoma cells with human high molecular weight-melanoma associated antigen-specific antibodies elicited by a peptide mimotope: functional effects. J Immunol 176(10):6046–6054PubMed
8.
Reynolds SR, Vergilis IJ, Szarek M, Ferrone S, Bystryn JC (2006) Cytoplasmic melanoma-associated antigen (CYT-MAA) serum level in patients with melanoma: a potential marker of response to immunotherapy? Int J Cancer 119(1):157–161PubMedCrossRef
9.
Vergilis IJ, Szarek M, Ferrone S, Reynolds SR (2005) Presence and prognostic significance of melanoma-associated antigens CYT-MAA and HMW-MAA in serum of patients with melanoma. J Invest Dermatol 125(3):526–531PubMedCrossRef
10.
Ulmer A, Fierlbeck G (2006) Circulating tumor cells and detection of the melanoma-associated antigen HMW-MAA in the serum of melanoma patients. J Invest Dermatol 126(4):914–915 author reply 915-916PubMedCrossRef
11.
Wagner S, Krepler C, Allwardt D, Latzka J, Strommer S, Scheiner O, Pehamberger H, Wiedermann U, Hafner C, Breiteneder H (2008) Reduction of human melanoma tumor growth in severe combined immunodeficient mice by passive transfer of antibodies induced by a high molecular weight melanoma-associated antigen mimotope vaccine. Clin Cancer Res 14(24):8178–8183PubMedCrossRef
12.
Maciag PC, Seavey MM, Pan ZK, Ferrone S, Paterson Y (2008) Cancer immunotherapy targeting the high molecular weight melanoma-associated antigen protein results in a broad antitumor response and reduction of pericytes in the tumor vasculature. Cancer Res 68(19):8066–8075PubMedCrossRef
13.
Tinari N, D’Egidio M, Iacobelli S, Bowen M, Starling G, Seachord C, Darveau R, Aruffo A (1997) Identification of the tumor antigen 90 K domains recognized by monoclonal antibodies SP2 and L3 and preparation and characterization of novel anti-90 K monoclonal antibodies. Biochem Biophys Res Commun 232(2):367–372PubMedCrossRef
14.
Grassadonia A, Tinari N, Iurisci I, Piccolo E, Cumashi A, Innominato P, D’Egidio M, Natoli C, Piantelli M, Iacobelli S (2004) 90 K (Mac-2 BP) and galectins in tumor progression and metastasis. Glycoconj J 19(7–9):551–556PubMed
15.
Fukaya Y, Shimada H, Wang LC, Zandi E, DeClerck YA (2008) Identification of galectin-3-binding protein as a factor secreted by tumor cells that stimulates interleukin-6 expression in the bone marrow stroma. J Biol Chem 283(27):18573–18581PubMedCrossRef
16.
Natali PG, Giacomini P, Russo C, Steinbach G, Fenoglio C, Ferrone S (1983) Antigenic profile of human melanoma cells. Analysis with monoclonal antibodies to histocompatibility antigens and to melanoma-associated antigens. J Cutan Pathol 10(4):225–237PubMedCrossRef
17.
Scambia G, Panici PB, Iacobelli S, Baiocchi G, Battaglia F, Perrone L, Sonsini C, Ferrandina G, Natoli C, Mancuso S (1990) Recombinant alpha-2b-interferon enhances the circulating levels of a 90-kilodalton (K) tumor-associated antigen in patients with gynecologic and breast malignancies. Cancer 65(6):1325–1328PubMedCrossRef
18.
Gray-Schopfer V, Wellbrock C, Marais R (2007) Melanoma biology and new targeted therapy. Nature 445(7130):851–857PubMedCrossRef
19.
Barker PA, Salehi A (2002) The MAGE proteins: emerging roles in cell cycle progression, apoptosis, and neurogenetic disease. J Neurosci Res 67(6):705–712PubMedCrossRef
20.
Castelli C, Rivoltini L, Andreola G, Carrabba M, Renkvist N, Parmiani G (2000) T-cell recognition of melanoma-associated antigens. J Cell Physiol 182(3):323–331PubMedCrossRef
21.
Epping MT, Bernards R (2006) A causal role for the human tumor antigen preferentially expressed antigen of melanoma in cancer. Cancer Res 66(22):10639–10642PubMedCrossRef
22.
Jungbluth AA, Chen YT, Stockert E, Busam KJ, Kolb D, Iversen K, Coplan K, Williamson B, Altorki N, Old LJ (2001) Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues. Int J Cancer 92(6):856–860PubMedCrossRef
23.
Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3(3):203–216PubMedCrossRef
24.
25.
Park JR, Eggert A, Caron H (2008) Neuroblastoma: biology, prognosis, and treatment. Pediatr Clin North Am 55(1):97–120PubMedCrossRef
26.
Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, De Bernardi B, Evans AE, Favrot M, Hedborg F et al (1993) Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 11(8):1466–1477PubMed
27.
Fischer M, Spitz R, Oberthur A, Westermann F, Berthold F (2008) Risk estimation of neuroblastoma patients using molecular markers. Klin Padiatr 220(3):137–146PubMedCrossRef
28.
Mora J, Gerald WL, Cheung NK (2003) Evolving significance of prognostic markers associated with new treatment strategies in neuroblastoma. Cancer Lett 197(1–2):119–124PubMedCrossRef
29.
Simon T, Hero B, Hunneman DH, Berthold F (2003) Tumour markers are poor predictors for relapse or progression in neuroblastoma. Eur J Cancer 39(13):1899–1903PubMedCrossRef
30.
Cecchetto G, Mosseri V, De Bernardi B, Helardot P, Monclair T, Costa E, Horcher E, Neuenschwander S, Toma P, Rizzo A, Michon J, Holmes K (2005) Surgical risk factors in primary surgery for localized neuroblastoma: the LNESG1 study of the European International Society of Pediatric Oncology Neuroblastoma Group. J Clin Oncol 23(33):8483–8489. doi:10.​1200/​JCO.​2005.​02.​4661 PubMedCrossRef
31.
Rubie H, De Bernardi B, Gerrard M, Canete A, Ladenstein R, Couturier J, Ambros P, Munzer C, Pearson AD, Garaventa A, Brock P, Castel V, Valteau-Couanet D, Holmes K, Di Cataldo A, Brichard B, Mosseri V, Marquez C, Plantaz D, Boni L, Michon J (2011) Excellent outcome with reduced treatment in infants with nonmetastatic and unresectable neuroblastoma without MYCN amplification: results of the prospective INES 99.1. J Clin Oncol 29(4):449–455. doi:10.​1200/​JCO.​2010.​29.​5196 PubMedCrossRef
32.
Olgun N, Kansoy S, Aksoylar S, Cetingul N, Vergin C, Oniz H, Sarialioglu F, Kantar M, Uysal K, Tuncyurek M, Kargi A, Aktas S, Bayol U, Karaca I, Arikan A, Balik E, Aktug T, Elmas N, Kovanlikaya A, Kinay M, Anacak Y, Degirmenci B, Burak Z (2003) Experience of the izmir pediatric oncology group on neuroblastoma: IPOG-NBL-92 protocol. Pediatr Hematol Oncol 20(3):211–218PubMed
33.
Brignole C, Pastorino F, Marimpietri D, Pagnan G, Pistorio A, Allen TM, Pistoia V, Ponzoni M (2004) Immune cell-mediated antitumor activities of GD2-targeted liposomal c-myb antisense oligonucleotides containing CpG motifs. J Natl Cancer Inst 96(15):1171–1180PubMedCrossRef
34.
Pastorino F, Mumbengegwi DR, Ribatti D, Ponzoni M, Allen TM (2008) Increase of therapeutic effects by treating melanoma with targeted combinations of c-myc antisense and doxorubicin. J Control Release 126(1):85–94PubMedCrossRef
35.
Chiesa S, Prigione I, Morandi F, Buoncompagni A, Picco P, Bocca P, Martini A, Pistoia V, Gattorno M (2004) Cytokine flexibility of early and differentiated memory T helper cells in juvenile idiopathic arthritis. J Rheumatol 31(10):2048–2054PubMed
36.
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408PubMedCrossRef
37.
Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39(4):561–577PubMed
38.
Corrias MV, Gambini C, Gregorio A, Croce M, Barisione G, Cossu C, Rossello A, Ferrini S, Fabbi M (2010) Different subcellular localization of ALCAM molecules in neuroblastoma: Association with relapse. Cell Oncol 32(1–2):77–86. doi:10.​3233/​CLO-2009-0494 PubMed
39.
Granchi D, Corrias MV, Garaventa A, Baglio SR, Cangemi G, Carlini B, Paolucci P, Giunti A, Baldini N (2011) Neuroblastoma and bone metastases: clinical significance and prognostic value of Dickkopf 1 plasma levels. Bone 48(1):152–159. doi:10.​1016/​j.​bone.​2010.​06.​028 PubMedCrossRef
40.
41.
Marchetti A, Tinari N, Buttitta F, Chella A, Angeletti CA, Sacco R, Mucilli F, Ullrich A, Iacobelli S (2002) Expression of 90 K (Mac-2 BP) correlates with distant metastasis and predicts survival in stage I non-small cell lung cancer patients. Cancer Res 62(9):2535–2539PubMed
42.
Gordower L, Decaestecker C, Kacem Y, Lemmers A, Gusman J, Burchert M, Danguy A, Gabius H, Salmon I, Kiss R, Camby I (1999) Galectin-3 and galectin-3-binding site expression in human adult astrocytic tumours and related angiogenesis. Neuropathol Appl Neurobiol 25(4):319–330PubMedCrossRef
43.
Ulmer TA, Keeler V, Loh L, Chibbar R, Torlakovic E, Andre S, Gabius HJ, Laferte S (2006) Tumor-associated antigen 90 K/Mac-2-binding protein: possible role in colon cancer. J Cell Biochem 98(5):1351–1366PubMedCrossRef
44.
Hajto T, Hostanska K, Frei K, Rordorf C, Gabius HJ (1990) Increased secretion of tumor necrosis factors alpha, interleukin 1, and interleukin 6 by human mononuclear cells exposed to beta-galactoside-specific lectin from clinically applied mistletoe extract. Cancer Res 50(11):3322–3326PubMed
45.
Inohara H, Akahani S, Koths K, Raz A (1996) Interactions between galectin-3 and Mac-2-binding protein mediate cell–cell adhesion. Cancer Res 56(19):4530–4534PubMed
46.
Pocza P, Suli-Vargha H, Darvas Z, Falus A (2008) Locally generated VGVAPG and VAPG elastin-derived peptides amplify melanoma invasion via the galectin-3 receptor. Int J Cancer 122(9):1972–1980. doi:10.​1002/​ijc.​23296 PubMedCrossRef
47.
Ara T, Song L, Shimada H, Keshelava N, Russell HV, Metelitsa LS, Groshen SG, Seeger RC, DeClerck YA (2009) Interleukin-6 in the bone marrow microenvironment promotes the growth and survival of neuroblastoma cells. Cancer Res 69(1):329–337PubMedCrossRef
48.
Ozaki Y, Kontani K, Teramoto K, Fujita T, Tezuka N, Sawai S, Watanabe H, Fujino S, Asai T, Ohkubo I (2004) Identification of antigenic epitopes recognized by Mac-2 binding protein-specific cytotoxic T lymphocytes for use in cancer immunotherapy. Biochem Biophys Res Commun 317(4):1089–1095. doi:10.​1016/​j.​bbrc.​2004.​03.​155 PubMedCrossRef
49.
Ozaki Y, Kontani K, Hanaoka J, Chano T, Teramoto K, Tezuka N, Sawai S, Fujino S, Yoshiki T, Okabe H, Ohkubo I (2002) Expression and immunogenicity of a tumor-associated antigen, 90 K/Mac-2 binding protein, in lung carcinoma. Cancer 95(9):1954–1962. doi:10.​1002/​cncr.​10899 PubMedCrossRef
Metadata
Title
Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients
Authors
Fabio Morandi
Maria Valeria Corrias
Isabella Levreri
Paola Scaruffi
Lizzia Raffaghello
Barbara Carlini
Paola Bocca
Ignazia Prigione
Sara Stigliani
Loredana Amoroso
Soldano Ferrone
Vito Pistoia
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 10/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-011-1052-0

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