Top

Published in:

01-04-2015 | Original Article

Serum metallothionein in patients with testicular cancer

Authors: Blanka Tariba, Tanja Živković, Nesrete Krasnići, Vlatka Filipović Marijić, Marijana Erk, Marija Gamulin, Mislav Grgić, Alica Pizent

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015

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.

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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

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 CrossRefPubMed

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

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

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMedCentralPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRef

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

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 CrossRefPubMed

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 57:561–566PubMed

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 CrossRef

20.

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

21.

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

22.

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

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 CrossRefPubMed

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 CrossRefPubMedCentralPubMed

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 91:306–311CrossRefPubMed

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

27.

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

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 CrossRefPubMedCentral

29.

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

30.

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

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 124:31–36CrossRefPubMed

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

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 85:777–781CrossRefPubMed

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 CrossRefPubMedCentralPubMed

35.

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

36.

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

37.

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

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 CrossRefPubMed

39.

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

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 CrossRefPubMedCentralPubMed

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 CrossRefPubMed

Title: Serum metallothionein in patients with testicular cancer
Authors: Blanka Tariba
Tanja Živković
Nesrete Krasnići
Vlatka Filipović Marijić
Marijana Erk
Marija Gamulin
Mislav Grgić
Alica Pizent
Publication date: 01-04-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2702-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2015

Hepatitis B virus reactivation and hepatitis in gastrointestinal cancer patients after chemotherapy

Delayed methotrexate excretion in infants and young children with central nervous system tumors and postoperative fluid collections

Germline TYMS genotype is highly predictive in patients with metastatic gastrointestinal malignancies receiving capecitabine-based chemotherapy

A randomized, crossover phase 1 study to assess the effects of formulation (capsule vs tablet) and meal consumption on the bioavailability of dovitinib (TKI258)

Prognostic value of ERCC1, RRM1, and TS proteins in patients with resected non-small cell lung cancer

A pharmacokinetic binding model for bevacizumab and VEGF165 in colorectal cancer patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer