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Overexpression of S100P promotes colorectal cancer metastasis and decreases chemosensitivity to 5-FU in vitro

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Abstract

S100P has been shown to be overexpressed in various cancers and to have putative involvement in the metastatic process. However, Clinical and pathological significance of S100P expression in colorectal cancer still needs to be further studied. In the present study, the method of immunohistochemistry was utilized to investigate S100P protein expression in 91 cases of colorectal cancer. Also, the influence of ectopic expression of S100P on the biologic behavior in SW480 colorectal cancer cells was studied. We found that S100P expression of colorectal cancer tissue was significantly higher than that of normal colorectal mucosal tissues. S100P expression showed to be significantly correlated with clinical staging, lymph node metastasis and recurrence. Ectopic expression of S100P promotes SW480 cancer cells migration and invasion, decreases chemosensitivity to 5-FU in vitro. These findings suggested that S100P could serve as a promising candidate for colorectal cancer marker, prognostic indicator, and therapeutic target.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58(2):71–96. doi:10.3322/CA.2007.0010

    Article  PubMed  Google Scholar 

  2. Lockhart-Mummery HE, Ritchie JK, Hawley PR (1976) The results of surgical treatment for carcinoma of the rectum of St Mark’s Hospital from 1948 to 1972. Br J Surg 63(9):673–677

    Article  CAS  PubMed  Google Scholar 

  3. Khair G, Monson JR, Greenman J (2007) Epithelial molecular markers in the peripheral blood of patients with colorectal cancer. Dis Colon Rectum 50(8):1188–1203. doi:10.1007/s10350-006-0875-9

    Article  PubMed  Google Scholar 

  4. Russell AH, Pelton J, Reheis CE, Wisbeck WM, Tong DY, Dawson LE (1985) Adenocarcinoma of the colon: an autopsy study with implications for new therapeutic strategies. Cancer 56(6):1446–1451

    Article  CAS  PubMed  Google Scholar 

  5. Jiang H, Hu H, Tong X, Jiang Q, Zhu H, Zhang S (2012) Calcium-binding protein S100P and cancer: mechanisms and clinical relevance. J Cancer Res Clin Oncol 138(1):1–9. doi:10.1007/s00432-011-1062-5

    Article  CAS  PubMed  Google Scholar 

  6. Tothova V, Gibadulinova A (2013) S100P, a peculiar member of S100 family of calcium-binding proteins implicated in cancer. Acta Virol 57(2):238–246

    Article  CAS  PubMed  Google Scholar 

  7. 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):1199–1207. doi:10.1158/0008-5472.CAN-05-2605

    Article  CAS  PubMed  Google Scholar 

  8. 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):1230–1240. doi:10.1007/s10350-006-0850-5

    Article  PubMed  Google Scholar 

  9. Dowen SE, Crnogorac-Jurcevic T, Gangeswaran R, Hansen M, Eloranta JJ, Bhakta V, Brentnall TA, Luttges J, Kloppel G, Lemoine NR (2005) Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer. Am J Pathol 166(1):81–92. doi:10.1016/S0002-9440(10)62234-1

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Barry S, Chelala C, Lines K, Sunamura M, Wang A, Marelli-Berg FM, Brennan C, Lemoine NR, Crnogorac-Jurcevic T (2013) S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells. Clin Exp Metastasis 30(3):251–264. doi:10.1007/s10585-012-9532-y

    Article  CAS  PubMed  Google Scholar 

  11. Chandramouli A, Mercado-Pimentel ME, Hutchinson A, Gibadulinova A, Olson ER, Dickinson S, Shanas R, Davenport J, Owens J, Bhattacharyya AK, Regan JW, Pastorekova S, Arumugam T, Logsdon CD, Nelson MA (2010) The induction of S100P expression by the Prostaglandin E(2) (PGE(2))/EP4 receptor signaling pathway in colon cancer cells. Cancer Biol Ther 10(10):1056–1066. doi:10.4161/cbt.10.10.13373

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Jiang L, Lai YK, Zhang J, Wang H, Lin MC, He ML, Kung HF (2011) Targeting S100P inhibits colon cancer growth and metastasis by Lentivirus-mediated RNA interference and proteomic analysis. Mol Med 17(7–8):709–716. doi:10.2119/molmed.2011.00008

    CAS  PubMed Central  PubMed  Google Scholar 

  13. McKiernan E, McDermott EW, Evoy D, Crown J, Duffy MJ (2011) The role of S100 genes in breast cancer progression. Tumour Biol 32(3):441–450. doi:10.1007/s13277-010-0137-2

    Article  CAS  PubMed  Google Scholar 

  14. Arumugam T, Logsdon CD (2011) S100P: a novel therapeutic target for cancer. Amino Acids 41(4):893–899. doi:10.1007/s00726-010-0496-4

    Article  CAS  PubMed  Google Scholar 

  15. Inti Zlobec RS, Terracciano Luigi, Jeremy R, Jass Alessandro Lugli (2007) Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol 60:1112–1116

    Article  PubMed Central  PubMed  Google Scholar 

  16. Jiang L, Lai YK, Zhang JF, Chan CY, Lu G, Lin MC, He ML, Li JC, Kung HF (2012) Transactivation of the TIEG1 confers growth inhibition of transforming growth factor-beta-susceptible hepatocellular carcinoma cells. World J Gastroenterol 18(17):2035–2042. doi:10.3748/wjg.v18.i17.2035

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Whiteman HJ, Weeks ME, Dowen SE, Barry S, Timms JF, Lemoine NR, Crnogorac-Jurcevic T (2007) The role of S100P in the invasion of pancreatic cancer cells is mediated through cytoskeletal changes and regulation of cathepsin D. Cancer Res 67(18):8633–8642. doi:10.1158/0008-5472.CAN-07-0545

    Article  CAS  PubMed  Google Scholar 

  18. Wang Q, Zhang YN, Lin GL, Qiu HZ, Wu B, Wu HY, Zhao Y, Chen YJ, Lu CM (2012) S100P, a potential novel prognostic marker in colorectal cancer. Oncol Rep 28(1):303–310. doi:10.3892/or.2012.1794

    PubMed  Google Scholar 

  19. Arumugam T, Simeone DM, Van Golen K, Logsdon CD (2005) S100P promotes pancreatic cancer growth, survival, and invasion. Clin Cancer Res 11(15):5356–5364. doi:10.1158/1078-0432.CCR-05-0092

    Article  CAS  PubMed  Google Scholar 

  20. 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):1806–1818. doi:10.1093/jnci/djj498

    Article  CAS  PubMed  Google Scholar 

  21. 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):1935–1943. doi:10.1016/j.ejca.2007.06.010

    Article  CAS  PubMed  Google Scholar 

  22. Parkkila S, Pan PW, Ward A, Gibadulinova A, Oveckova I, Pastorekova S, Pastorek J, Martinez AR, Helin HO, Isola J (2008) The calcium-binding protein S100P in normal and malignant human tissues. BMC Clin Pathol 8:2. doi:10.1186/1472-6890-8-2

    Article  PubMed Central  PubMed  Google Scholar 

  23. 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):541–547

    Article  CAS  PubMed  Google Scholar 

  24. Sato N, Hitomi J (2002) S100P expression in human esophageal epithelial cells: human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation. Anat Rec 267(1):60–69. doi:10.1002/ar.10085

    Article  CAS  PubMed  Google Scholar 

  25. Birkenkamp-Demtroder K, Olesen SH, Sorensen FB, Laurberg S, Laiho P, Aaltonen LA, Orntoft TF (2005) Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut 54(3):374–384. doi:10.1136/gut.2003.036848

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Averboukh L, Liang P, Kantoff PW, Pardee AB (1996) Regulation of S100P expression by androgen. Prostate 29(6):350–355. doi:10.1002/(SICI)1097-0045(199612)29:6<350::AID-PROS2>3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  27. Onyeagucha BC, Mercado-Pimentel ME, Hutchison J, Flemington EK, Nelson MA (2013) S100P/RAGE signaling regulates microRNA-155 expression via AP-1 activation in colon cancer. Exp Cell Res 319(13):2081–2090. doi:10.1016/j.yexcr.2013.05.009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Emberley ED, Murphy LC, Watson PH (2004) S100 proteins and their influence on pro-survival pathways in cancer. Biochem Cell Biol 82(4):508–515. doi:10.1139/o04-052

    Article  CAS  PubMed  Google Scholar 

  29. Ge F, Wang C, Wang W, Wu B (2013) S100P predicts prognosis and drug resistance in gastric cancer. Int J Biol Markers. doi:10.5301/jbm.5000034

    PubMed  Google Scholar 

  30. Longley DB, Harkin DP, Johnston PG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3(5):330–338. doi:10.1038/nrc1074

    Article  CAS  PubMed  Google Scholar 

  31. Akao Y, Noguchi S, Iio A, Kojima K, Takagi T, Naoe T (2011) Dysregulation of microRNA-34a expression causes drug-resistance to 5-FU in human colon cancer DLD-1 cells. Cancer Lett 300(2):197–204. doi:10.1016/j.canlet.2010.10.006

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81101823), Zhejiang Provincial Natural Science Foundation of China (Y2100018), Medicine and Health Technology Program of Zhejiang Province (2013KYA129), Wenzhou Science and Technology Bureau Program (Y20100017), and Qianjiang Talents Project of Zhejiang Province (2011R10058).

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China

    Lei Dong

  2. Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China

    Fule Wang, Feiyan Lin, Wuhua Ni, Jianbo Wu & Lei Jiang

  3. Department of Pathology, Jiaxing Maternity and Child Health Care Hopital, Jiaxing, 314051, Zhejiang, People’s Republic of China

    Xiaona Yin

  4. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, People’s Republic of China

    Ling Chen

  5. Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China

    Gang Li

  6. Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China

    Rong Jin

  7. Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China

    Rong Jin

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  1. Lei Dong
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  2. Fule Wang
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Correspondence to Rong Jin or Lei Jiang.

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Dong, L., Wang, F., Yin, X. et al. Overexpression of S100P promotes colorectal cancer metastasis and decreases chemosensitivity to 5-FU in vitro. Mol Cell Biochem 389, 257–264 (2014). https://doi.org/10.1007/s11010-013-1947-5

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  • DOI: https://doi.org/10.1007/s11010-013-1947-5

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