Measurement of Total Iron in Breast Tissue Samples by Inductively Coupled Plasma-Mass Spectrometry
Yıl 2023,
Cilt: 82 Sayı: 2, 270 - 279, 21.12.2023
Mete Bora Tüzüner
,
Burcin Tüzüner
Öz
Objective: Breast cancer is the commonest and the deadliest malignancy among women. Iron is known as an essential element for cell growth and division. The connection between oxidative stress, antioxidants, and progression, aggressiveness, and recurrence of breast cancer, is widely recognized to involve impaired iron metabolism. The purpose of this study was to investigate the connection between the tumor characteristics and the levels of total iron in breast tissues by employing state of the art technology, inductively-coupled plasma/mass spectrometry (ICP-MS) with our in-house analysis methodology for tissue samples.
Materials and Methods: Iron contents were determined in 25 tissue sets (matched tumor and peritumoral tissues) collected from 25 women diagnosed with invasive ductal breast cancer. In addition, three cancer-free breast tissues, obtained from breast reduction surgery, were analyzed as a normal group. Collected samples were digested and introduced to ICP-MS for iron analysis.
Results: Our method showed a low rate of measurement error (<10%). A highly significant (p<0.001) ∼3 fold difference of iron concentrations were observed in tumors (24.73±6.15 ppb/mg) as compared to peritumoral tissues (9.10±4.84 ppb/mg). As the grade and stage of the cancer increases, iron levels in tumor tissues were also found to be increased (p=0.006, p=0.022 respectively).
Conclusion: Our ICP-MS based method can be reliably performed at the established conditions for tissue specimens, and also have potential to be used in clinical practice. Understanding the relationship between tissue iron levels and tumor characteristics is essential in identifying potential prevention and treatment strategies.
Teşekkür
Tülin Öztürk and Şennur İlvan from Department of Pathology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpaşa, for access to breast tissue samples and histopathological evaluation. Jülide Coşkun for her expert technical support with ICP-MS analysis. Fehime Aksungar from Department of Basic Sciences, Medical Biochemistry, School of Medicine for useful discussions and invaluable opinions during the optimization process of the experiments.
Kaynakça
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- Shpyleva SI, Tryndyak VP, Kovalchuk O, et al. Role of ferritin alterations in human breast cancer cells. Breast Cancer Res Treat. 2011;126:63-71. google scholar
- Toyokuni S. Iron-induced carcinogenesis: The role of redox reg-ulation. Free Radic Biol Med. 1996;20(4):553-566. google scholar
- Nelson RL. Dietary iron and colorectal cancer risk. Free Radic Biol Med. 1992;12(2):161-168. google scholar
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- Benhar M, Engelberg D, Levitzki A. ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep. 2002;3(5):420-425. google scholar
- Kowdley KV. Iron, hemochromatosis, and hepatocellular carci-noma. Gastroenterology. 2004;127(5 Suppl 1):S79-86. google scholar
- Galaris D, Skiada V, Barbouti A. Redox signaling and cancer: the role of “labile” iron. Cancer Lett. 2008;266(1):21-29. google scholar
- Cermak J, Balla J, Jacob HS, et al. Tumor cell heme uptake induces ferritin synthesis resulting in altered oxidant sensitivity: possible role in chemotherapy efficacy. Cancer Res. 1993;53(21):5308-5313. google scholar
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- Whitmire M, Osredkar A, Ammerman J, et al. Full validation of a high resolution ICP-MS bioanalysis method for iron in hu-man plasma with K2EDTA. J Chromatograph Separat Techniq. 2011;S4:001. doi:10.4172/2157-7064.S4-001. google scholar
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- Marjania A, kbari FA, Eshghinia S. Association between trace elements and metabolic syndrome among type 2 diabetes mellitus patients in Gorgan. Asian J Pharm Clin Res. 2015;8(3): 358-363. google scholar
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- Enders A, Lehmann J. Comparison of wet digestion and dry ashing methods for total elemental analysis of biochar. Commun Soil Sci Plant Anal. 2012;43(4): 1042-1052. google scholar
- Vanhoe H . A review of the capabilities of ICP-MS for trace element analysis in body fluids and tissues. J Trace Elem Electrolytes Health Dis. 1993;7(3):131-139. google scholar
- Takahashi SI, Takahashi H. Sato, Kubota Y, Yoshida S, Mura-matsu Y. Determination of major and trace elements in the liver of Wistar rats by inductively coupled plasma-atomic emission spectrometry and mass spectrometry. Lab Animal. 2000;34(1): 97-105. google scholar
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- Sharma M, Beck AH, Webster JA, et al. Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ. Breast Cancer Res Treat. 2010;123:397-404. google scholar
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- Tuzuner MB, Ozturk T, Ilvan S, et al. Local aromatase activ-ity alterations in breast cancer tissues: A potential way of de-cision support for clinicians. Exp Mol Pathol.2021;118:104574. doi: 10.1016/j.yexmp.2020.104574. google scholar
- Simpson ER. Sources of estrogen and their importance. J Steroid Biochem Mol Biol. 2003; 86(3-5):225-230. google scholar
- Lonning PE, Haynes BP, Straume AH, et al. Recent data on intra-tumor estrogens in breast cancer. Steroids. 2011;76(8):786-791. google scholar
- Bajbouj K, Shafarin J, Abdalla MY, Ahmad I, Hamad M. Estrogen-induced disruption of intracellular iron metabolism leads to oxidative stress, membrane damage, and cell cy-cle arrest in MCF-7 cells. Tumor Biol. 2017;39:1-12. doi: 10.1177/1010428317726184. google scholar
- Cavalieri E, Chakravarti D, Guttenplan J, et al. Catechol estrogen quinones as initiators of breast and other human cancers: Impli-cations for biomarkers of susceptibility and cancer prevention. Biochim Biophys Acta. 2006;1766:63-78. google scholar
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Yıl 2023,
Cilt: 82 Sayı: 2, 270 - 279, 21.12.2023
Mete Bora Tüzüner
,
Burcin Tüzüner
Kaynakça
- Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol. 2022;95(1130): 20211033. doi:10.1259/bjr.20211033. google scholar
- Guo Q, Li L, Hou S, et al. The role of iron in cancer progression. Front Oncol. 2021;11:778492. doi: 10.3389/fonc.2021.778492. google scholar
- Thompson HJ, Kennedy K, Witt M, Juzefyk J. Effect of di-etary iron deficiency or excess on the induction of mam-mary carcinogenesis by 1-methyl-1-nitrosourea. Carcinogenesis. 1991;12:111-114. google scholar
- Singh M, Lu J, Briggs SP, McGinley JN, Haegele AD, Thompson HJ. Effect of excess dietary iron on the promotion stage of 1-methyl-1-nitrosourea-induced mammary carcinogenesis: patho-genetic characteristics and distribution of iron. Carcinogenesis. 1994;15:1567-1570. google scholar
- Hrabinski D, Hertz JL, Tantillo C, Berger V, Sherman AR. Iron repletion attenuates the protective effects of iron defi-ciency in DMBA-induced mammary tumors in rats. Nutr Cancer. 1995;24:133-142. google scholar
- Diwan BA, Kasprzak KS, Anderson LM. Promotion of dimethylbenz[a]anthracene-initiated mammary carcinogenesis by iron in female Sprague-Dawley rats. Carcinogenesis. 1997;18:1757-1762. google scholar
- Huang X. Does iron have a role in breast cancer? Lancet Oncol. 2008;9:803-807. google scholar
- Cui Y, Vogt S, Olson N, Glass AG, Rohan TE. Levels of zinc, selenium, calcium, and iron in benign breast tissue and risk of subsequent breast cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:1682-1685. google scholar
- Elliott RL, Elliott MC, Wang F, Head JF. Breast carcinoma and the role of iron metabolism. A cytochemical, tissue culture, and ultrastructural study. Ann N Y Acad Sci. 1993;698:159-166. google scholar
- Miller LD, Coffman LG, Chou JW, et al. An iron regulatory gene signature predicts outcome in breast cancer. Cancer Res. 2011;71:6728-6737. google scholar
- Shpyleva SI, Tryndyak VP, Kovalchuk O, et al. Role of ferritin alterations in human breast cancer cells. Breast Cancer Res Treat. 2011;126:63-71. google scholar
- Toyokuni S. Iron-induced carcinogenesis: The role of redox reg-ulation. Free Radic Biol Med. 1996;20(4):553-566. google scholar
- Nelson RL. Dietary iron and colorectal cancer risk. Free Radic Biol Med. 1992;12(2):161-168. google scholar
- Eaton JW, Qian M. Molecular bases of cellular iron toxicity. Free Radic Biol Med. 2002;32(9):833-840. google scholar
- Benhar M, Engelberg D, Levitzki A. ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep. 2002;3(5):420-425. google scholar
- Kowdley KV. Iron, hemochromatosis, and hepatocellular carci-noma. Gastroenterology. 2004;127(5 Suppl 1):S79-86. google scholar
- Galaris D, Skiada V, Barbouti A. Redox signaling and cancer: the role of “labile” iron. Cancer Lett. 2008;266(1):21-29. google scholar
- Cermak J, Balla J, Jacob HS, et al. Tumor cell heme uptake induces ferritin synthesis resulting in altered oxidant sensitivity: possible role in chemotherapy efficacy. Cancer Res. 1993;53(21):5308-5313. google scholar
- Omary MB, Trowbridge IS, Minowada J. Human cell-surface gly-coprotein with unusual properties. Nature. 1980:286(5776):888-891. google scholar
- Brookes MJ, Hughes S, Turner FE, et al. Modulation of iron transport proteins in human colorectal carcinogenesis. Gut. 2006;55(10):1449-1460. google scholar
- Boult J, Roberts K, Brookes MJ, et al. Overexpression of cellular iron import proteins is associated with malignant progression of esophageal adenocarcinoma. Clin. Cancer Res.2008;14(2):379-387. google scholar
- Gulcin İ. Antioxidants and antioxidant methods: An updated overview. Arch Toxicol. 2020;94:651-715. google scholar
- Khurana RK, Jain A, Jain A, Sharma T, Singh B, Kesharwani P. Administration of antioxidants in cancer: Debate of the decade. Drug Discov Today. 2018;23:763-770. google scholar
- Athreya K, Xavier MF. Antioxidants in the treatment of cancer. Nutr Cancer. 2017;69: 1099-1104. google scholar
- Sarmiento-Salinas FL, Delgado-Magallon A, Cortes-Hernandez P, Reyes-Leyva J, Herrera-Camacho I. Breast cancer subtypes present a differential production of reactive oxygen species (ROS) and susceptibility to antioxidant treatment. Front Oncol. 2019;9:1-13. doi: 10.3389/fonc.2019.00480. google scholar
- Gill JG, Piskounova E, Morrison SJ. Cancer, oxidative stress, and metastasis. Cold Spring Harb Symp Quant Biol. 2016;81:163-175. google scholar
- Satheesh NJ, Samuel SM, Büsselberg D. Combination therapy with vitamin C could eradicate cancer stem cells. Biomolecules. 2020;10:79. doi: 10.3390/biom10010079. google scholar
- Mohsin AR, Khan UH, Akbar B. Evaluation of post radiotherapy antioxidants levels in cancer patients. Asian J Multidiscip Stud. 2019;7:2348-7186. google scholar
- Jung AY, Cai X, Thoene K, et al. Antioxidant supplementa-tion and breast cancer prognosis in postmenopausal women un-dergoing chemotherapy and radiation therapy. Am J Clin Nutr. 2019;109:69-78. google scholar
- Dastmalchi N, Baradaran B, Latifi-Navid S, et al. Antioxidants with two faces toward cancer. Life Sci. 2020;258:118186. doi: 10.1016/j.lfs.2020.118186. google scholar
- Bonner MY, Arbiser JL. The antioxidant paradox: What are an-tioxidants and how should they be used in a therapeutic context for cancer. Future Med Chem. 2014; 6:1413-1422. google scholar
- Ambrosone, C.B. Review article oxidants and antioxidants in breast cancer. Antioxid Redox Signal. 2000;2:903-917. google scholar
- Zacharski LR, Ornstein DL, Woloshin S, Schwartz LM. Associa-tion of age, sex, and race with body iron stores in adults: Analysis of NHANES III data. Am Heart J. 2000;140(1):98-104. google scholar
- Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006;160(1):1-40. doi: 10.1016/j.cbi.2005.12.009. google scholar
- Whitmire M, Osredkar A, Ammerman J, et al. Full validation of a high resolution ICP-MS bioanalysis method for iron in hu-man plasma with K2EDTA. J Chromatograph Separat Techniq. 2011;S4:001. doi:10.4172/2157-7064.S4-001. google scholar
- An introduction to the fundamentals of inductively cou-pled plasma-mass spectrometry (ICP-MS) facts. Agi-lent website. https://www.agilent.com/en/product/atomic-spectroscopy/inductively-coupled-plasma-mass-spectrometry-icp-ms/what-is-icp-ms-icp-ms-faqs. Accessed June 8, 2023. google scholar
- Badran M, Morsy R, Soliman H, Elnimr T. Assessment of wet acid digestion methods for ICP-MS determination of trace elements in biological samples by using Multivariate Statistical Analysis. J Elem. 2018;23(1):179-189. google scholar
- Imam MU, Zhang S, Ma J, Wang H, Wang F. Antioxidants mediate both iron homeostasis and oxidative stress. Nutrients. 2017;9(7): 671. doi: 10.3390/nu9070671. google scholar
- Mertz W. The essential trace elements. Science.1981;213(4514):1332-1338. google scholar
- Malakar R, Kour M, Ahmed A, Malviya SN, Dangi CBS. Trace elements ratio in patients of haemoglobinopathie. Int J Curr Mi-crobiol App Sci. 2014;3(6):81-92. google scholar
- Marjania A, kbari FA, Eshghinia S. Association between trace elements and metabolic syndrome among type 2 diabetes mellitus patients in Gorgan. Asian J Pharm Clin Res. 2015;8(3): 358-363. google scholar
- Badran M, Morsy R, Soliman H, Elnimr T. Assessment of trace elements levels in patients with Type 2 diabetes using Multivariate Statistical Analysis. J Trace Elem Med Bio. 2016;33:114-119. google scholar
- Iyengar VG, Subramanian KS, Joost RW. Element Analysis of Biological Samples, Principles and Practice. 1st ed. Woittiez, Boca Raton.;FL:CRC Press. 1998:137. google scholar
- Becker JS, Dietze HJ. State-of-the-art in inorganic mass spectrom-etry for analysis of high-purity materials. Int J Mass Spectrom. 2003;228(2):127-150. google scholar
- McComb JQ, Rogers C, Han FX, Tchounwou PB. Rapid screen-ing of heavy metals and trace elements in environmental sam-ples using portable X-ray fluorescence spectrometer, A com-parative study. Water Air Soil Pollut. 2014;225(12):1-10. doi: 10.1007/s11270-014-2169-5. google scholar
- Dressler VL,Antes FG, Moreira CM, Pozebon D, Andrei Duarte F. As, Hg, I, Sb, Se and Sn speciation in body fluids and bio-logical tissues using hyphenated-ICP-MS techniques. Int J Mass Spectrom. 2011;307(1-3):149-162. google scholar
- Enders A, Lehmann J. Comparison of wet digestion and dry ashing methods for total elemental analysis of biochar. Commun Soil Sci Plant Anal. 2012;43(4): 1042-1052. google scholar
- Vanhoe H . A review of the capabilities of ICP-MS for trace element analysis in body fluids and tissues. J Trace Elem Electrolytes Health Dis. 1993;7(3):131-139. google scholar
- Takahashi SI, Takahashi H. Sato, Kubota Y, Yoshida S, Mura-matsu Y. Determination of major and trace elements in the liver of Wistar rats by inductively coupled plasma-atomic emission spectrometry and mass spectrometry. Lab Animal. 2000;34(1): 97-105. google scholar
- Hseu ZY. Evaluating heavy metal contents in nine composts using four digestion methods. Biores Technol. 2004;95(1): 53-59. google scholar
- Hansen THK, Laursen H, Persson DP, Pedas P, Husted S, Schjo-erring JK. Microscaled high-throughput digestion of plant tissue samples for multi-elemental analysis. Plant Methods. 2009;5(1): 5-12. google scholar
- Liu M, Okada S. Induction of free radicals and tumors in the kidney of Wistar rats by ferric ethylendiaminbe-N,N’-diacetate. Int J Sports Med. 1996;17: 397-403. google scholar
- Mello FA, Meneghini R. In vivo formation of single-strand breaks in DNA by hydrogen peroxide is mediated by the Haber-Weissreaction. Biochem Biophys Acta. 1984;781: 56-63. google scholar
- Okada S. Iron-induced tissue damage and cancer: The role of re-active oxygen species and free radicals. Pathol Int. 1996;46:311-332. google scholar
- Weinberg ED. The role of iron in cancer. Eur J Cancer Prev. 1996;5: 19-36. google scholar
- Ionescu JG, Novotny J, Stejskal V, Latsch A, Blaurock-Busch E, Eisenmann-Klein M. Increased levels of transition metals in breast cancer tissue. Neuro Endocrinol Lett. 2006;27 (Suppl. 1):36-39. google scholar
- Cui Y, Vogt S, Olson N, Glass AG, Rohan TE. Levels of zinc, selenium, calcium, and iron in benign breast tissue and risk of subsequent breast cancer. Cancer Epidemiol Biomarkers Prev. 2007;16:1682-1685. google scholar
- Marques O, Porto G, Rema A, et al. Local iron homeostasis in the breast ductal carcinoma microenvironment. BMC cancer. 2016;16(1):1-14. doi: 10.1186/s12885-016-2228-y. google scholar
- Sharma M, Beck AH, Webster JA, et al. Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ. Breast Cancer Res Treat. 2010;123:397-404. google scholar
- Ma XJ, Dahiya S, Richardson E, Erlander M, Sgroi DC. Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res. 2009;11:R7. doi: 10.1186/bcr2222. google scholar
- Pinnix ZK, Miller LD, Wang W, et al. Ferroportin and iron regu-lation in breast cancer progression and prognosis. Sci Transl Med. 2010;2(43):43ra56. doi: 10.1126/scitranslmed.3001127. google scholar
- Kwok JC, Richardson DR. The iron metabolism of neoplastic cells: alterations that facilitate proliferation?. Crit Rev Oncol Hematol. 2002;42(1):65-78. google scholar
- Tuzuner MB, Ozturk T, Ilvan S, et al. Local aromatase activ-ity alterations in breast cancer tissues: A potential way of de-cision support for clinicians. Exp Mol Pathol.2021;118:104574. doi: 10.1016/j.yexmp.2020.104574. google scholar
- Simpson ER. Sources of estrogen and their importance. J Steroid Biochem Mol Biol. 2003; 86(3-5):225-230. google scholar
- Lonning PE, Haynes BP, Straume AH, et al. Recent data on intra-tumor estrogens in breast cancer. Steroids. 2011;76(8):786-791. google scholar
- Bajbouj K, Shafarin J, Abdalla MY, Ahmad I, Hamad M. Estrogen-induced disruption of intracellular iron metabolism leads to oxidative stress, membrane damage, and cell cy-cle arrest in MCF-7 cells. Tumor Biol. 2017;39:1-12. doi: 10.1177/1010428317726184. google scholar
- Cavalieri E, Chakravarti D, Guttenplan J, et al. Catechol estrogen quinones as initiators of breast and other human cancers: Impli-cations for biomarkers of susceptibility and cancer prevention. Biochim Biophys Acta. 2006;1766:63-78. google scholar
- Jian J, Yang Q, Dai J, et al. Effects of iron deficiency and iron overload on angiogenesis and oxidative stress—A potential dual role for iron in breast cancer. Free Radic Biol Med. 2011;50: 841-847. google scholar