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Targeted Mass Spectrometry of S100 Proteins

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Calcium-Binding Proteins of the EF-Hand Superfamily

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1929))

Abstract

The S100 protein family has attracted great interest in the field of biomarker research, and a growing number of studies reveal dysregulation of many of the 21 S100 protein isoforms in various human diseases. In cancer, S100 protein expression has been associated with tumor growth, progression, and response to treatment. Some S100 proteins are also considered candidate therapeutic targets. From an analytical perspective, multiplexed analysis of the family-wide S100 protein expression is challenging due to their relatively small size and high-sequence identity. Here we describe a mass spectrometry method using selected reaction monitoring which enables the targeted, multiplexed detection and quantitation of the entire S100 protein family in cell lines and tissue samples.

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References

  1. Marenholz I, Heizmann CW, Fritz G (2004) S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature). Biochem Biophys Res Commun 322(4):1111–1122. https://doi.org/10.1016/j.bbrc.2004.07.096

    Article  CAS  PubMed  Google Scholar 

  2. Salama I, Malone PS, Mihaimeed F et al (2008) A review of the S100 proteins in cancer. Eur J Surg Oncol 34(4):357–364. https://doi.org/10.1016/j.ejso.2007.04.009

    Article  CAS  PubMed  Google Scholar 

  3. Chen H, Xu C, Jin Q et al (2014) S100 protein family in human cancer. Am J Cancer Res 4(2):89–115

    PubMed  PubMed Central  Google Scholar 

  4. Gupta S, Hussain T, MacLennan GT et al (2003) Differential expression of S100A2 and S100A4 during progression of human prostate adenocarcinoma. J Clin Oncol 21(1):106–112. https://doi.org/10.1200/jco.2003.03.024

    Article  CAS  PubMed  Google Scholar 

  5. Cho YG, Kim CJ, Nam SW et al (2005) Overexpression of S100A4 is closely associated with progression of colorectal cancer. World J Gastroenterol 11(31):4852–4856. https://doi.org/10.3748/wjg.v11.i31.4852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Huang LY, Xu Y, Cai GX et al (2011) S100A4 over-expression underlies lymph node metastasis and poor prognosis in colorectal cancer. World J Gastroenterol 17(1):69–78. https://doi.org/10.3748/wjg.v17.i1.69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang XH, Zhang LH, Zhong XY et al (2010) S100A6 overexpression is associated with poor prognosis and is epigenetically up-regulated in gastric cancer. Am J Pathol 177(2):586–597. https://doi.org/10.2353/ajpath.2010.091217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. De Petris L, Orre LM, Kanter L et al (2009) Tumor expression of S100A6 correlates with survival of patients with stage I non-small-cell lung cancer. Lung Cancer 63(3):410–417. https://doi.org/10.1016/j.lungcan.2008.06.003

    Article  PubMed  Google Scholar 

  9. Shekouh AR, Thompson CC, Prime W et al (2003) Application of laser capture microdissection combined with two-dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma. Proteomics 3(10):1988–2001. https://doi.org/10.1002/pmic.200300466

    Article  CAS  PubMed  Google Scholar 

  10. Al-Haddad S, Zhang Z, Leygue E et al (1999) Psoriasin (S100A7) expression and invasive breast cancer. Am J Pathol 155(6):2057–2066. https://doi.org/10.1016/s0002-9440(10)65524-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Arai K, Takano S, Teratani T et al (2008) S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast. Curr Cancer Drug Targets 8(4):243–252. https://doi.org/10.2174/156800908784533445

    Article  CAS  PubMed  Google Scholar 

  12. Anania MC, Miranda C, Vizioli MG et al (2013) S100A11 overexpression contributes to the malignant phenotype of papillary thyroid carcinoma. J Clin Endocrinol Metab 98(10):E1591–E1600. https://doi.org/10.1210/jc.2013-1652

    Article  CAS  PubMed  Google Scholar 

  13. Arumugam T, Simeone DM, Van Golen K et al (2005) S100P promotes pancreatic cancer growth, survival, and invasion. Clin Cancer Res 11(15):5356–5364. https://doi.org/10.1158/1078-0432.Ccr-05-0092

    Article  CAS  PubMed  Google Scholar 

  14. Martinez-Aguilar J, Clifton-Bligh R, Molloy MP (2015) A multiplexed, targeted mass spectrometry assay of the S100 protein family uncovers the isoform-specific expression in thyroid tumours. BMC Cancer 15:199. https://doi.org/10.1186/s12885-015-1217-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Memon AA, Sorensen BS, Meldgaard P et al (2005) Down-regulation of S100C is associated with bladder cancer progression and poor survival. Clin Cancer Res 11(2 Pt 1):606–611

    CAS  PubMed  Google Scholar 

  16. Bachet JB, Marechal R, Demetter P et al (2013) S100A2 is a predictive biomarker of adjuvant therapy benefit in pancreatic adenocarcinoma. Eur J Cancer 49(12):2643–2653. https://doi.org/10.1016/j.ejca.2013.04.017

    Article  CAS  PubMed  Google Scholar 

  17. Azimi A, Pernemalm M, Frostvik Stolt M et al (2014) Proteomics analysis of melanoma metastases: association between S100A13 expression and chemotherapy resistance. Br J Cancer 110(10):2489–2495. https://doi.org/10.1038/bjc.2014.169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gogas H, Eggermont AMM, Hauschild A et al (2009) Biomarkers in melanoma. Ann Oncol 20(suppl 6):vi8–vi13. https://doi.org/10.1093/annonc/mdp251

    Article  PubMed  PubMed Central  Google Scholar 

  19. Vandesompele J, De Preter K, Pattyn F et al. (2002 Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3 (7):Research0034. doi:https://doi.org/10.1186/gb-2002-3-7-research0034

    Article  Google Scholar 

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Acknowledgments

MPM acknowledges support from the Cancer Institute NSW and Sydney Vital Translational Cancer Research Centre.

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Correspondence to Mark P. Molloy .

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Martínez-Aguilar, J., Molloy, M.P. (2019). Targeted Mass Spectrometry of S100 Proteins. In: Heizmann, C. (eds) Calcium-Binding Proteins of the EF-Hand Superfamily. Methods in Molecular Biology, vol 1929. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9030-6_41

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  • DOI: https://doi.org/10.1007/978-1-4939-9030-6_41

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9029-0

  • Online ISBN: 978-1-4939-9030-6

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