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Serum metallothionein in patients with testicular cancer

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Abstract

Purpose

Metallothioneins (MTs) have been disclosed as a useful diagnostic factor for tumour progression and drug resistance in a variety of malignancies. Increased levels of MT in blood serum have been found in patients with several types of cancer, but there is no available information on serum MT levels in patients with testicular germ cell tumour (TGCT). The aim of the study was to determine MT levels in serum of patients with TGCT and to evaluate the portion of platinum (Pt) that binds to MT after cisplatin administration since MTs could be involved in drug resistance.

Methods

Concentration of total MT was determined in serum of 25 men with newly diagnosed TGCT by differential pulse voltammetry. The fractionation of serum was carried out by size exclusion high-performance liquid chromatography (SE-HPLC), while concentration of Pt in collected fractions was determined by inductively coupled plasma mass spectrometry.

Results

Concentration of serum MT was significantly higher in TGCT patients than in healthy volunteers. The results of SE-HPLC analysis showed that only a small amount of Pt was bound to proteins in the area of MT elution.

Conclusions

Significant increase in MT levels in individuals with TGCT indicates certain health problem and, in combination with other commonly used diagnostic tools, could improve early diagnosis.

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References

  1. Purdue MP, Devesa SS, Sigurdson AJ, McGlynn KA (2005) International patterns and trends in testis cancer incidence. Int J Cancer 115:822–827. doi:10.1002/ijc.20931

    Article  CAS  PubMed  Google Scholar 

  2. Bray F, Richiardi L, Ekbom A, Pukkala E, Cuninkova M, Møller H (2006) Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality. Int J Cancer 118:3099–3111. doi:10.1002/ijc.21747

    Article  CAS  PubMed  Google Scholar 

  3. Huyghe E, Matsuda T, Thonneau P (2003) Increasing incidence of testicular cancer worldwide: a review. J Urol 170:5–11. doi:10.1097/01.ju.0000053866.68623.da

    Article  PubMed  Google Scholar 

  4. Sincic N, Kulis T, Znaor A, Bray F (2012) Time trends in testicular cancer in Croatia 1983–2007: rapid increases in incidence, no declines in mortality. Cancer Epidemiol 36:11–15. doi:10.1016/j.canep.2011.09.010

    Article  PubMed  Google Scholar 

  5. Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2013) SEER cancer statistics review, 1975–2011. National Cancer Institute, Bethesda. http://seer.cancer.gov/csr/1975_2011/. Accessed 1 Dec 2014

  6. García-Velasco A, Durán I, García E, Tarón M, Ballestín C, Castellanos D, Cortés-Funés H, Paz-Ares L (2012) Biological markers of cisplatin resistance in advanced testicular germ cell tumours. Clin Transl Oncol 14:452–457. doi:10.1007/s12094-012-0823-1

    Article  PubMed  Google Scholar 

  7. American Joint Committee on Cancer (AJCC) (2010) Cancer staging manual, 7th edn. Springer Science and Business Media LLC (SBM), Berlin

    Book  Google Scholar 

  8. Vasdev N, Thorpe A (2012) Testicular germ cell tumours: a European and UK perspective. Germ cell tumor, Dr. Angabin Matin (ed), ISBN: 978-953-51-0456-8, InTech. http://www.intechopen.com/books/germ-cell-tumor/testicular-germ-cell-tumour

  9. Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca P (2006) Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 101:513–523. doi:10.1111/j.1572-0241.2006.00467.x

    Article  CAS  PubMed  Google Scholar 

  10. Kim HS, Lee HE, Yang H-K, Kim WH (2014) High lactate dehydrogenase 5 expression correlates with high tumoral and stromal vascular endothelial growth factor expression in gastric cancer. Pathobiology 81:78–85. doi:10.1159/000357017

    Article  CAS  PubMed  Google Scholar 

  11. Jin R (2002) Metallothionein 2A expression is associated with cell proliferation in breast cancer. Carcinogenesis 23:81–86. doi:10.1093/carcin/23.1.81

    Article  CAS  PubMed  Google Scholar 

  12. Weinlich G, Eisendle K, Hassler E, Baltaci M, Fritsch PO, Zelger B (2006) Metallothionein—overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients. Br J Cancer 94:835–841. doi:10.1038/sj.bjc.6603028

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Schmitz KJ, Müller CI, Reis H et al (2009) Combined analysis of hypoxia-inducible factor 1 alpha and metallothionein indicates an aggressive subtype of colorectal carcinoma. Int J Colorectal Dis 24:1287–1296. doi:10.1007/s00384-009-0753-8

    Article  PubMed  Google Scholar 

  14. Pontes HAR, de Aquino Xavier FC, da Silva TSP, Fonseca FP, Paiva HB, Pontes FSC, Jr Dos Santos Pinto D (2009) Metallothionein and p-Akt proteins in oral dysplasia and in oral squamous cell carcinoma: an immunohistochemical study. J Oral Pathol Med 38:644–650. doi:10.1111/j.1600-0714.2009.00787.x

    Article  CAS  PubMed  Google Scholar 

  15. Fabrik I, Krizkova S, Huska D, Adam V, Hubalek J, Trnkova L, Eckschlager T, Kukacka J, Prusa R, Kizek R (2008) Employment of electrochemical techniques for metallothionein determination in tumor cell lines and patients with a tumor disease. Electroanalysis 20:1521–1532. doi:10.1002/elan.200704215

    Article  CAS  Google Scholar 

  16. Krejcova L, Fabrik I, Hynek D, Krizkova S, Gumulec J, Ryvolova M, Adam V, Babula P, Trnkova L, Stiborova M, Hubalek J, Masarik M, Binkova H, Eckschlager T, Kizek R (2012) Metallothionein electrochemically determined using Brdicka reaction as a promising blood marker of head and neck malignant tumours. Int J Electrochem Sci 7:1767–1784

    CAS  Google Scholar 

  17. Krizkova S, Ryvolova M, Gumulec J, Masarik M, Adam V, Majzlik P, Hubalek J, Provaznik I, Kizek R (2011) Electrophoretic fingerprint metallothionein analysis as a potential prostate cancer biomarker. Electrophoresis 32:1952–1961. doi:10.1002/elps.201000519

    Article  CAS  PubMed  Google Scholar 

  18. Krizkova S, Masarik M, Majzlik P, Kukacka J, Kruseova J, Adam V, Prusa R, Eckschlager T, Stiborova M, Kizek R (2010) Serum metallothionein in newly diagnosed patients with childhood solid tumours. Acta Biochim Pol 57:561–566

    CAS  PubMed  Google Scholar 

  19. Capdevila M, Bofill R, Palacios O, Atrian S (2012) State-of-the-art of metallothioneins at the beginning of the 21st century. Coord Chem Rev 256:46–62. doi:10.1016/j.ccr.2011.07.006

    Article  CAS  Google Scholar 

  20. Thirumoorthy N, Manisenthil Kumar KT, Shyam Sundar A, Panayappan L, Chatterjee M (2007) Metallothionein: an overview. World J Gastroenterol 13:993–996

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Siddik ZH (2003) Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22:7265–7279. doi:10.1038/sj.onc.1206933

    Article  CAS  PubMed  Google Scholar 

  22. Raspor B (2001) Elucidation of the mechanism of the Brdicka reaction. J Electroanal Chem 503:159–162

    Article  CAS  Google Scholar 

  23. Martinčič A, Cemazar M, Sersa G, Kovač V, Milačič R, Ščančar J (2013) A novel method for speciation of Pt in human serum incubated with cisplatin, oxaliplatin and carboplatin by conjoint liquid chromatography on monolithic disks with UV and ICP-MS detection. Talanta 116:141–148. doi:10.1016/j.talanta.2013.05.016

    Article  PubMed  Google Scholar 

  24. Holding J, Lindup W, van Laer C, Vreeburg GC, Schilling V, Wilson JA, Stell PM (1992) Phase I trial of a cisplatin-albumin complex for the treatment of cancer of the head and neck. Br J Clin Pharmacol 33:75–81. doi:10.1111/j.1365-2125.1992.tb04003.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Peleg-Shulman T, Najajreh Y, Gibson D (2002) Interactions of cisplatin and transplatin with proteins. Comparison of binding kinetics, binding sites and reactivity of the Pt-protein adducts of cisplatin and transplatin towards biological nucleophiles. J Inorg Biochem 91:306–311

    Article  CAS  PubMed  Google Scholar 

  26. Hsu M, Wang W, Li L (2014) Lower level of serum metallothionein I/II in patients with atopic dermatitis. Austin J Dermatol 1:2–3

    Google Scholar 

  27. Russo AJ (2009) Anti-metallothionein IgG and levels of metallothionein in autistic children with GI disease. Drug Healthc Patient Saf 1:1–8

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Krizkova S, Fabrik I, Adam V, Kukacka J, Prusa R, Chavis GJ, Trnkova L, Strnadel J, Horak V, Kizek R (2008) Utilizing of adsorptive transfer stripping technique Brdicka reaction for determination of metallothioneins level in melanoma cells, blood serum and tissues. Sensors 8:3106–3122. doi:10.3390/s8053106

    Article  PubMed Central  CAS  Google Scholar 

  29. Nordberg M, Nordberg GF (2009) Metallothioneins: historical development and overview. Met Ions Life Sci 5:1–29. doi:10.1039/9781847558992-00001

    Article  CAS  Google Scholar 

  30. Kontozoglou TE, Banerjee D, Cherian MG (1989) Immunohistochemical localization of metallothionein in human testicular embryonal carcinoma cells. Virchows Arch A Pathol Anat Histopathol 415:545–549

    Article  CAS  PubMed  Google Scholar 

  31. Eid H, Géczi L, Bodrogi I, Institoris E, Bak M (1998) Do metallothioneins affect the response to treatment in testis cancers? J Cancer Res Clin Oncol 124:31–36

    Article  CAS  PubMed  Google Scholar 

  32. Chin JL, Banerjee D, Kadhim SA, Kontozoglou TE, Chauvin PJ, Cherian MG (1993) Metallothionein in testicular germ cell tumors and drug resistance. Clin Correl Cancer 72:3029–3035

    CAS  Google Scholar 

  33. Meijer C, Timmer A, De Vries EG, Groten JP, Knol A, Zwart N, Dam WA, Sleijfer D, Mulder NH (2000) Role of metallothionein in cisplatin sensitivity of germ-cell tumours. Int J Cancer 85:777–781

    Article  CAS  PubMed  Google Scholar 

  34. Gumulec J, Raudenska M, Adam V, Kizek R, Masarik M (2014) Metallothionein—immunohistochemical cancer biomarker: a meta-analysis. PLoS One 9:e85346. doi:10.1371/journal.pone.0085346

    Article  PubMed Central  PubMed  Google Scholar 

  35. Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Pérez JM (2007) Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem 7:3–18

    Article  CAS  PubMed  Google Scholar 

  36. Desoize B, Madoulet C (2002) Particular aspects of platinum compounds used at present in cancer treatment. Crit Rev Oncol Hematol 42:317–325

    Article  PubMed  Google Scholar 

  37. DeConti RC, Toftness BR, Lange RC, Creasey WA (1973) Clinical and pharmacological studies with cis-diamminedichloroplatinum(II). Cancer Res 33:1310–1315

    CAS  PubMed  Google Scholar 

  38. Michalke B (2010) Platinum speciation used for elucidating activation or inhibition of Pt-containing anti-cancer drugs. J Trace Elem Med Biol 24:69–77. doi:10.1016/j.jtemb.2010.01.006

    Article  CAS  PubMed  Google Scholar 

  39. Hagrman D, Goodisman J, Dabrowiak JC, Souid AK (2003) Kinetic study on the reaction of cisplatin with metallothionein. Drug Metab Dispos 31:916–923

    Article  CAS  PubMed  Google Scholar 

  40. Huska D, Fabrik I, Baloun J, Adam V, Masarik M, Hubalek J, Vasku A, Trnkova L, Horna A, Zeman L, Kizek R (2009) Study of interactions between metallothionein and cisplatin by using differential pulse voltammetry Brdicka reaction and quartz crystal microbalance. Sensors 9:1355–1369. doi:10.3390/s90301355

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Ossipov K, Scaffidi-Domianello YY, Seregina IF, Galanski M, Keppler BK, Timerbaev AR, Bolshov MA (2014) Inductively coupled plasma mass spectrometry for metallodrug development: albumin binding and serum distribution of cytotoxic cis- and trans-isomeric platinum(II) complexes. J Inorg Biochem 137:40–45. doi:10.1016/j.jinorgbio.2014.04.008

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the Croatian Ministry of Science, Education and Sports (Grant Number 022-0222411-2408).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All procedures performed in this study involving human participants were in accordance with the ethical standards of institutional ethics committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Authors and Affiliations

  1. Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, POB 291, 10000, Zagreb, Croatia

    Blanka Tariba, Tanja Živković & Alica Pizent

  2. Division for Marine and Environmental Research, Laboratory for Biological Effects of Metals, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia

    Nesrete Krasnići, Vlatka Filipović Marijić & Marijana Erk

  3. Department of Oncology, Clinical Hospital Centre Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia

    Marija Gamulin & Mislav Grgić

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  1. Blanka Tariba
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  2. Tanja Živković
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  3. Nesrete Krasnići
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Correspondence to Blanka Tariba.

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Tariba, B., Živković, T., Krasnići, N. et al. Serum metallothionein in patients with testicular cancer. Cancer Chemother Pharmacol 75, 813–820 (2015). https://doi.org/10.1007/s00280-015-2702-2

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  • DOI: https://doi.org/10.1007/s00280-015-2702-2

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