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Amino Acids

, Volume 41, Issue 4, pp 893–899 | Cite as

S100P: a novel therapeutic target for cancer

  • Thiruvengadam Arumugam
  • Craig D. LogsdonEmail author
Review Article

Abstract

S100P expression is described in many different cancers, and its expression is associated with drug resistance, metastasis, and poor clinical outcome. S100P is member of the S100 family of small calcium-binding proteins that have been reported to have either intracellular or extracellular functions, or both. Extracellular S100P can bind with the receptor for advanced glycation end products (RAGE) and activate cellular signaling. Through RAGE, S100P has been shown to mediate tumor growth, drug resistance, and metastasis. S100P is specifically expressed in cancer cells in the adult. Therefore, S100P is a useful marker for differentiating cancer cells from normal cells, and can aid in the diagnosis of cancer by cytological examination. The expression of S100P in cancer cells has been related to hypomethylation of the gene. Multiple studies have confirmed the beneficial effects of blocking S100P/RAGE in cancer cells, and different blockers are being developed including small molecules and antagonist peptides. This review summarizes the role and significance of S100P in different cancers.

Keywords

S100P RAGE Calcium-binding protein Cancer Cromolyn 

Notes

Acknowledgments

This work was supported in part by the Marc Rich Foundation, the M.D. Anderson Support Core grant CA16672, the M.D. Anderson Pancreatic Specialized Programs of Research Excellence (SPORE) grant P20 CA101936, the Lockton Endowment and by Public Health Service Grant DK56338, which funds the Texas Medical Center Digestive Diseases Center.

References

  1. Amler LC, Agus DB, LeDuc C, Sapinoso ML, Fox WD, Kern S, Lee D, Wang V, Leysens M, Higgins B, Martin J, Gerald W, Dracopoli N, Cordon-Cardo C, Scher HI, Hampton GM (2000) Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22–R1. Cancer Res 60(21):6134–6141PubMedGoogle Scholar
  2. Arlt A, Vorndamm J, Breitenbroich M, Folsch UR, Kalthoff H, Schmidt WE et al (2001) Inhibition of NF-kappaB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin. Oncogene 20:859–868PubMedCrossRefGoogle Scholar
  3. Arumugam T, Simeone DM, Schmidt AM, Logsdon CD (2004) S100P stimulates cell proliferation and survival via receptor for activated glycation end products (RAGE). J Biol Chem 279(7):5059–5065PubMedCrossRefGoogle Scholar
  4. Arumugam T, Simeone DM, Van Golen K, Logsdon CD (2005) S100P promotes pancreatic cancer growth, survival, and invasion. Clin Cancer Res 11(15):5356–5364PubMedCrossRefGoogle Scholar
  5. Arumugam T, Ramachandran V, Logsdon CD (2006) Effect of cromolyn on S100P interactions with RAGE and pancreatic cancer growth and invasion in mouse models. J Natl Cancer Inst 98(24):1806–1818PubMedCrossRefGoogle Scholar
  6. Austermann J, Nazmi AR, Müller-Tidow C, Gerke V (2008) Characterization of the Ca2+-regulated ezrin-S100P interaction and its role in tumor cell migration. J Biol Chem 283(43):29331–29340PubMedCrossRefGoogle Scholar
  7. Averboukh L, Liang P, Kantoff PW, Pardee AB (1996) Regulation of S100P expression by androgen. Prostate 29(6):350–355PubMedCrossRefGoogle Scholar
  8. Bartling B, Rehbein G, Schmitt WD, Hofmann HS, Silber RE, Simm A (2007) S100A2–S100P expression profile and diagnosis of non-small cell lung carcinoma: impairment by advanced tumour stages and neoadjuvant chemotherapy. Eur J Cancer 43(13):1935–1943PubMedCrossRefGoogle Scholar
  9. Basu GD, Azorsa DO, Kiefer JA, Rojas AM, Tuzmen S, Barrett MT, Trent JM, Kallioniemi O, Mousses S (2008) Functional evidence implicating S100P in prostate cancer progression. Int J Cancer 123(2):330–339PubMedCrossRefGoogle Scholar
  10. Becker T, Gerke V, Kube E, Weber K (1992) S100P, a novel Ca(2+)-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties. Eur J Biochem 207(2):541–547PubMedCrossRefGoogle Scholar
  11. Bertram J, Palfner K, Hiddemann W, Kneba M (1998) Elevated expression of S100P, CAPL and MAGE 3 in doxorubicin-resistant cell lines: comparison of mRNA differential display reverse transcription-polymerase chain reaction and subtractive suppressive hybridization for the analysis of differential gene expression. Anticancer Drugs 9(4):311–317PubMedCrossRefGoogle Scholar
  12. Brodersen DE, Etzerodt M, Madsen P, Celis JE, Thøgersen HC, Nyborg J, Kjeldgaard M (1998) EF-hands at atomic resolution: the structure of human psoriasin (S100A7) solved by MAD phasing. Structure 6(4):477–489PubMedCrossRefGoogle Scholar
  13. Bulk E, Hascher A, Liersch R, Mesters RM, Diederichs S, Sargin B, Gerke V, Hotfilder M, Vormoor J, Berdel WE, Serve H, Müller-Tidow C (2008) Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung cancer metastasis development in mice. Cancer Res 68(6):1896–1904PubMedCrossRefGoogle Scholar
  14. Crnogorac-Jurcevic T, Missiaglia E, Blaveri E, Gangeswaran R, Jones M, Terris B, Costello E, Neoptolemos JP, Lemoine NR (2003) Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent. J Pathol 201(1):63–74PubMedCrossRefGoogle Scholar
  15. Dairkee SH, Sayeed A, Luciani G, Champion S, Meng Z, Jakkula LR, Feiler HS, Gray JW, Moore DH (2009) Immutable functional attributes of histologic grade revealed by context-independent gene expression in primary breast cancer cells. Cancer Res 69(19):7826–7834PubMedCrossRefGoogle Scholar
  16. Deng H, Shi J, Wilkerson M, Meschter S, Dupree W, Lin F (2008) Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle aspiration biopsy specimens. Am J Clin Pathol 129(1):81–88PubMedCrossRefGoogle Scholar
  17. Diederichs S, Bulk E, Steffen B, Ji P, Tickenbrock L, Lang K, Zänker KS, Metzger R, Schneider PM, Gerke V, Thomas M, Berdel WE, Serve H, Müller-Tidow C (2004) S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res 64(16):5564–5569PubMedCrossRefGoogle Scholar
  18. Dizdar O, Altundag K (2009) Emerging drugs in metastatic breast cancer. Expert Opin Emerg Drugs 14(1):85–98 ReviewPubMedCrossRefGoogle Scholar
  19. Donato R (1999) Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. Biochim Biophys Acta 1450(3):191–231 reviewPubMedCrossRefGoogle Scholar
  20. Dowen SE, Crnogorac-Jurcevic T, Gangeswaran R, Hansen M, Eloranta JJ, Bhakta V, Brentnall TA, Lüttges J, Klöppel G, Lemoine NR (2005) Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer. Am J Pathol 166(1):81–92PubMedCrossRefGoogle Scholar
  21. Fuentes MK, Nigavekar SS, Arumugam T, Logsdon CD, Schmidt AM, Park JC, Huang EH (2007) RAGE activation by S100P in colon cancer stimulates growth, migration, and cell signaling pathways. Dis Colon Rectum 50(8):1230–1240PubMedCrossRefGoogle Scholar
  22. Fukushima N, Sato N, Prasad N, Leach SD, Hruban RH, Goggins M (2004) Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays. Oncogene 23(56):9042–9051PubMedCrossRefGoogle Scholar
  23. Grothey A, Galanis E (2009) Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol 6(9):507–518PubMedCrossRefGoogle Scholar
  24. Guerreiro Da Silva ID, Hu YF, Russo IH, Ao X, Salicioni AM, Yang X, Russo J (2000) S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo. Int J Oncol 16(2):231–240PubMedGoogle Scholar
  25. Hamada S, Satoh K, Hirota M, Fujibuchi W, Kanno A, Umino J, Ito H, Satoh A, Kikuta K, Kume K, Masamune A, Shimosegawa T (2009) Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines. Cancer Sci 100(1):103–110PubMedCrossRefGoogle Scholar
  26. Hartmann JT, Haap M, Kopp HG, Lipp HP (2009) Tyrosine kinase inhibitors—a review on pharmacology, metabolism and side effects. Curr Drug Metab 10(5):470–481PubMedCrossRefGoogle Scholar
  27. Higgins JP, Kaygusuz G, Wang L, Montgomery K, Mason V, Zhu SX, Marinelli RJ, Presti JC Jr, van de Rijn M, Brooks JD (2007) Placental S100 (S100P) and GATA3: markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray. Am J Surg Pathol 31(5):673–680PubMedCrossRefGoogle Scholar
  28. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58(2):71–96PubMedCrossRefGoogle Scholar
  29. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310PubMedCrossRefGoogle Scholar
  30. Kim B, Lee HJ, Choi HY, Shin Y, Nam S, Seo G, Son DS, Jo J, Kim J, Lee J, Kim J, Kim K, Lee S (2007) Clinical validity of the lung cancer biomarkers identified by bioinformatics analysis of public expression data. Cancer Res 67(15):7431–7438PubMedCrossRefGoogle Scholar
  31. Kita H, Hikichi Y, Hikami K, Tsuneyama K, Cui ZG, Osawa H, Ohnishi H, Mutoh H, Hoshino H, Bowlus CL, Yamamoto H, Sugano K (2006) Differential gene expression between flat adenoma and normal mucosa in the colon in a microarray analysis. J Gastroenterol 41(11):1053–1063PubMedCrossRefGoogle Scholar
  32. Kupferman ME, Patel V, Sriuranpong V, Amornphimoltham P, Jasser SA, Mandal M, Zhou G, Wang J, Coombes K, Multani A, Pathak S, Silvio Gutkind J, Myers JN (2007) Molecular analysis of anoikis resistance in oral cavity squamous cell carcinoma. Oral Oncol 43(5):440–454PubMedCrossRefGoogle Scholar
  33. Leone-Bay A, Leipold H, Sarubbi D, Variano B, Rivera T, Baughman RA (1996) Oral delivery of sodium cromolyn: preliminary studies in vivo and in vitro. Pharm Res 13(2):222–226PubMedCrossRefGoogle Scholar
  34. Li Y, St John MA, Zhou X, Kim Y, Sinha U, Jordan RC, Eisele D, Abemayor E, Elashoff D, Park NH, Wong DT (2004) Salivary transcriptome diagnostics for oral cancer detection. Clin Cancer Res 10(24):8442–8450PubMedCrossRefGoogle Scholar
  35. Liang J, Luo G, Ning X, Shi Y, Zhai H, Sun S, Jin H, Liu Z, Zhang F, Lu Y, Zhao Y, Chen X, Zhang H, Guo X, Wu K, Fan D (2007) Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein. Biochem Cell Biol 85(3):375–383PubMedCrossRefGoogle Scholar
  36. Logsdon CD, Simeone DM, Binkley C, Arumugam T, Greenson JK, Giordano TJ, Misek DE, Kuick R, Hanash S (2003) Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res 63(10):2649–2657 erratum 63(12):3445PubMedGoogle Scholar
  37. Logsdon CD, Fuentes MK, Huang EH, Arumugam T (2007) RAGE and RAGE ligands in cancer. Curr Mol Med 7(8):777–789 ReviewPubMedCrossRefGoogle Scholar
  38. Mackay A, Jones C, Dexter T, Silva RL, Bulmer K, Jones A, Simpson P, Harris RA, Jat PS, Neville AM, Reis LF, Lakhani SR, O’Hare MJ (2003) cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells. Oncogene 22(17):2680–2688PubMedCrossRefGoogle Scholar
  39. Martinelli E, De Palma R, Orditura M, De Vita F, Ciardiello F (2009) Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin Exp Immunol 158(1):1–9 reviewPubMedCrossRefGoogle Scholar
  40. Mebratu Y, Tesfaigzi Y (2009) How ERK1/2 activation controls cell proliferation and cell death: is subcellular localization the answer? Cell Cycle 8(8):1168–1175 ReviewPubMedCrossRefGoogle Scholar
  41. Mesa RA (2006) Tipifarnib: farnesyl transferase inhibition at a crossroads. Expert Rev Anticancer Ther 6(3):313–319PubMedCrossRefGoogle Scholar
  42. Milde-Langosch K, Janke S, Wagner I, Schröder C, Streichert T, Bamberger AM, Jänicke F, Löning T (2008) Role of Fra-2 in breast cancer: influence on tumor cell invasion and motility. Breast Cancer Res Treat 107(3):337–347PubMedCrossRefGoogle Scholar
  43. Missiaglia E, Blaveri E, Terris B, Wang YH, Costello E, Neoptolemos JP, Crnogorac-Jurcevic T, Lemoine NR (2004) Analysis of gene expression in cancer cell lines identifies candidate markers for pancreatic tumorigenesis and metastasis. Int J Cancer 112(1):100–112PubMedCrossRefGoogle Scholar
  44. Moore BW (1965) A soluble protein characteristic of the nervous system. Biochem Biophys Res Commun 19(6):739–744PubMedCrossRefGoogle Scholar
  45. Mousses S, Bubendorf L, Wagner U, Hostetter G, Kononen J, Cornelison R, Goldberger N, Elkahloun AG, Willi N, Koivisto P, Ferhle W, Raffeld M, Sauter G, Kallioniemi OP (2002) Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays. Cancer Res 62(5):1256–1260PubMedGoogle Scholar
  46. Namba T, Homan T, Nishimura T, Mima S, Hoshino T, Mizushima T (2009) Up-regulation of S100P expression by non-steroidal anti-inflammatory drugs and its role in anti-tumorigenic effects. J Biol Chem 284(7):4158–4167PubMedCrossRefGoogle Scholar
  47. Oesterling J, Fuks Z, Lee C, Scher HI (1997) Cancer of the prostate. In: Dvita VT, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 5th edn. Lippincott-Raven, Philadelphia, pp 1322–1386Google Scholar
  48. Ohuchida K, Mizumoto K, Egami T, Yamaguchi H, Fujii K, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M (2006) S100P is an early developmental marker of pancreatic carcinogenesis. Clin Cancer Res 12(18):5411–5416PubMedCrossRefGoogle Scholar
  49. Okada M, Tokumitsu H, Kubota Y, Kobayashi R (2002) Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem Biophys Res Commun 292(4):1023–1030PubMedCrossRefGoogle Scholar
  50. Pliarchopoulou K, Pectasides D (2009) Pancreatic cancer: current and future treatment strategies. Cancer Treat Rev 35(5):431–436PubMedCrossRefGoogle Scholar
  51. Rayet B, Gélinas C (1999) Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18(49):6938–6947PubMedCrossRefGoogle Scholar
  52. Rehbein G, Simm A, Hofmann HS, Silber RE, Bartling B (2008) Molecular regulation of S100P in human lung adenocarcinomas. Int J Mol Med 22(1):69–77PubMedGoogle Scholar
  53. Réty S, Sopkova J, Renouard M, Osterloh D, Gerke V, Tabaries S, Russo-Marie F, Lewit-Bentley A (1999) The crystal structure of a complex of p11 with the annexin II N-terminal peptide. Nat Struct Biol 6(1):89–95PubMedCrossRefGoogle Scholar
  54. Réty S, Osterloh D, Arié JP, Tabaries S, Seeman J, Russo-Marie F, Gerke V, Lewit-Bentley A (2000) Structural basis of the Ca(2+)-dependent association between S100C (S100A11) and its target, the N-terminal part of annexin I. Structure 8(2):175–184PubMedCrossRefGoogle Scholar
  55. Sato N, Fukushima N, Matsubayashi H, Goggins M (2004) Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene 23(8):1531–1538PubMedCrossRefGoogle Scholar
  56. Schäfer BW, Wicki R, Engelkamp D, Mattei MG, Heizmann CW (1995) Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family. Genomics 25(3):638–643PubMedCrossRefGoogle Scholar
  57. Schor AP, Carvalho FM, Kemp C, Silva ID, Russo J (2006) S100P calcium-binding protein expression is associated with high-risk proliferative lesions of the breast. Oncol Rep 15(1):3–6PubMedGoogle Scholar
  58. Shishibori T, Oyama Y, Matsushita O, Yamashita K, Furuichi H, Okabe A, Maeta H, Hata Y, Kobayashi R (1999) Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family. Biochem J 338(Pt 3):583–589PubMedCrossRefGoogle Scholar
  59. Shyu RY, Huang SL, Jiang SY (2003) Retinoic acid increases expression of the calcium-binding protein S100P in human gastric cancer cells. J Biomed Sci 10(3):313–319PubMedCrossRefGoogle Scholar
  60. Sparvero LJ, Asafu-Adjei D, Kang R, Tang D, Amin N, Im J, Rutledge R, Lin B, Amoscato AA, Zeh HJ, Lotze MT (2009) RAGE (receptor for advanced glycation endproducts), RAGE ligands, and their role in cancer and inflammation. J Transl Med 7:17 ReviewPubMedCrossRefGoogle Scholar
  61. Surowiak P, Maciejczyk A, Materna V, Drag-Zalesińska M, Wojnar A, Pudelko M, Kedzia W, Spaczyński M, Dietel M, Zabel M, Lage H (2007) Unfavourable prognostic significance of S100P expression in ovarian cancers. Histopathology 51(1):125–128PubMedCrossRefGoogle Scholar
  62. Tsumura H, Akimoto M, Kiyota H, Ishii Y, Ishikura H, Honma Y (2009) Gene expression profiles in differentiating leukemia cells induced by methyl jasmonate are similar to those of cytokinins and methyl jasmonate analogs induce the differentiation of human leukemia cells in primary culture. Leukemia 23(4):753–760PubMedCrossRefGoogle Scholar
  63. Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR, Chiao PJ (1999) The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res 5:119–127PubMedGoogle Scholar
  64. Wang G, Platt-Higgins A, Carroll J, de Silva Rudland S, Winstanley J, Barraclough R, Rudland PS (2006) Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients. Cancer Res 66(2):1199–1207PubMedCrossRefGoogle Scholar
  65. Zhang H, Wang G, Ding Y, Wang Z, Barraclough R, Rudland PS, Fernig DG, Rao Z (2003) The crystal structure at 2A resolution of the Ca2+-binding protein S100P. J Mol Biol 325(4):785–794PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Cancer BiologyUT MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Medical OncologyUT MD Anderson Cancer CenterHoustonUSA

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