期刊论文详细信息
Cancer Cell International
Psoriasin (S100A7) is a novel biomarker for lung squamous cell carcinoma in humans
Jihong Zhang3  Xueying Song2  Guilan Liu3  Qiang Wu3  Guijuan Liu1 
[1] Department of Cytology Laboratory, People’s Hospital of Linyi, Linyi 276300, Shandong, China;Department of Thoracic Surgery, the People’s Hospital of Rizhao, Rizhao, China;Department of Nursing, People’s Hospital of Yinan, Linyi 276300, Shandong, China
关键词: NF-κB;    S100A7;    Lung squamous cell carcinoma;   
Others  :  1138482
DOI  :  10.1186/s12935-014-0154-0
 received in 2014-09-19, accepted in 2014-12-27,  发布年份 2015
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【 摘 要 】

Objective

Psoriasin (S100A7) plays a role in the malignant potential of several epithelial cancers, and could candidate diagnostic marker or therapeutic target. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. In the present study, we first evaluate the involvement of S100A7 in lung squamous cell carcinoma and its clinical usefulness for diagnosis. We then study whether knockdown of S100A7 in lung squamous cell carcinoma cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo.

Methods

We examined S100A7 expression in lung squamous cell carcinoma tissues by immunohistology. The human lung squamous cell carcinoma cell line NCI-H520 were transduced with short hairpin RNA targeting S100A7. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of S100A7 messenger RNA and protein, respectively. Cell proliferation was evaluated by the MTT assay. NF-κB phosphorylation was assayed by western blot. 1 × 106 of NCI-H520/S100A7 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 35 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for S100A7 protein expression.

Results

S100A7 protein levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. S100A7 might be a useful marker for diagnosis of lung squamous cell carcinoma. In vitro data showed that inhibition of S100A7 decreased proliferation of NCI-H520 cells. S100A7 knockdown reduced NF-κB phosphorylation and tumor growth in vivo and vivo. Explanted knockdown tumors maintained lower S100A7 levels compared with wild-type, confirmed by immunohistology. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors.

Conclusions

Our present results suggest that S100A7 level is a promising tool for diagnosis of lung squamous cell carcinoma. Knockdown of S100A7 suppresses lung cancer growth in part by attenuating NF-κB activity. S100A7 may be a promising therapeutic target for lung squamous cell carcinoma.

【 授权许可】

   
2015 Liu et al.; licensee BioMed Central.

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【 参考文献 】
  • [1]Moubayed N, Weichenthal M, Harder J, Wandel E, Sticherling M: Psoriasin (S100A7) is significantly up-regulated in human epithelial skin tumours. J Cancer Res Clin Oncol 2007, 133:253-61.
  • [2]Alowami S, Qing G, Emberley E, Snell L, Watson PH: S100A7 expression is altered during skin tumorigenesis. BMC Dermatol 2007, 3:1. BioMed Central Full Text
  • [3]Webb M, Emberley ED, Lizardo M, Alowami S, Qing G: Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis. BMC Cancer 2005, 5:17. BioMed Central Full Text
  • [4]Ostergaard M, Rasmussen HH, Nielsen HV, Vorum H, Orntoft TF: Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation. Cancer Res 1997, 57:4111-7.
  • [5]Al-Haddad S, Zhang Z, Leygue E, Snell L, Huang A: S100A7 expression and invasive breast cancer. Am J Pathol 1999, 155:2057-66.
  • [6]Zhang H, Zhao Q, Chen Y, Wang Y, Gao S, Mao Y, et al.: Selective expression of S100A7 in lung squamous cell carcinomas and large cell carcinomas but not in adenocarcinomas and small cell carcinomas. Thorax 2008, 63:352-9.
  • [7]Zhang H, Wang Y, Chen Y, Sun S, Li N, Lv D, et al.: Identification and validation of S100A7 associated with lung squamous cell carcinoma metastasis to brain. Lung Cancer 2007, 57:37-45.
  • [8]Karin M, Cao Y, Greten FR, Li ZW: NF-κB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002, 2:301-10.
  • [9]Tanabe T, Tohnai N: Cyclooxygenase isozymes and their gene structures and expression. Prostaglandins Other Lipid Mediat 2002, 68:95-114.
  • [10]Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L: IL-1β mediated up-regulation of HIF-1α via an NFkB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB J 2003, 17:2115-7.
  • [11]Liu H, Wang L, Wang X, Cao Z, Yang Q, Zhang K: S100A7 enhances invasion of human breast cancer MDA-MB-468 cells through activation of nuclear factor-κB signaling. World J Surg Oncol 2013, 11:93. BioMed Central Full Text
  • [12]Nguyen TT, Niyonsaba F, Ushio H, Akiyama T, Kiatsurayanon C, Smithrithee R, et al.: Interleukin-36 cytokines enhance the production of host defense peptides psoriasin and LL-37 by human keratinocytes through activation of MAPKs and NF-κB. J Dermatol Sci 2012, 68:63-6.
  • [13]WHO: Histological typing of lung and pleural tumours. 3rd edition. Springer-Verlag, Geneva (Switzerland); 1999.
  • [14]Sobin LH, Wittekind C: TNM classification of malignant tumors. 6th edition. Wiley, New York; 2002.
  • [15]Ovstebo R, Haug KB, Lande K, Kierulf P: PCR-based calibration curves for studies of quantitative gene expression in human monocytes: development and evaluation. Clin Chem 2003, 49:425-32.
  • [16]Chu YW, Yang PC, Yang SC: Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. Am J Respir Cell Mol Biol 1997, 17:353-60.
  • [17]Schafer BW, Heizmann CW: The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci 1996, 21:134-40.
  • [18]Madsen P, Rasmussen HH, Leffers H, Honore B, Dejgaard K, Olsen E, et al.: Molecular cloning, occurrence, and expression of a novel partially secreted protein ‘psoriasin’ that is highly up-regulated in psoriatic skin. J Invest Dermatol 1991, 97:701-12.
  • [19]Hoffmann HJ, Olsen E, Etzerodt M, Madsen P, Thogersen HC, Kruse T, et al.: Psoriasin binds calcium and is upregulated by calcium to levels that resemble those observed in normal skin. J Invest Dermatol 1994, 103:370-5.
  • [20]Jinquan T, Vorum H, Larsen CG, Madsen P, Rasmussen HH, Gesser B, et al.: Psoriasin: a novel chemotactic protein. J Invest Dermatol 1996, 107:5-10.
  • [21]Watson PH, Leygue ER, Murphy LC: Psoriasin (S100A7). Int J Biochem Cell Biol 1998, 30:567-71.
  • [22]Alowami S, Qing G, Emberley E, Snell L, Watson PH: Psoriasin (S100A7) expression is altered during skin tumorigenesis. BMC Dermatol 2003, 3:1. BioMed Central Full Text
  • [23]Celis JE, Rasmussen HH, Vorum H, Madsen P, Honore B, Wolf H, et al.: Bladder squamous cell carcinomas express psoriasin and externalize it to the urine. J Urol 1996, 155:2105-12.
  • [24]El Rifai W, Moskaluk CA, Abdrabbo MK, Harper J, Yoshida C, Riggins GJ, et al.: Gastric cancers overexpress S100A calcium-binding proteins. Cancer Res 2002, 62:6823-6.
  • [25]Enerback C, Porter DA, Seth P, Sgroi D, Gaudet J, Weremowicz S, et al.: Psoriasin expression in mammary epithelial cells in vitro and in vivo. Cancer Res 2002, 62:43-7.
  • [26]Leygue E, Snell L, Hiller T, Dotzlaw H, Hole K, Murphy LC, et al.: Differential expression of psoriasin messenger RNA between in situ and invasive human breast carcinoma. Cancer Res 1996, 56:4606-9.
  • [27]Marek L, Ware KE, Fritzsche A, Hercule P, Helton WR, Smith JE, et al.: Fibroblast growth fact (FGF) and FGF receptor-mediated autocrine signaling in non-small-cell lung cancer cells. Mol Pharmacol 2009, 75:196-207.
  • [28]Khromova N, Kopnin P, Rybko V, Kopnin BP: Downregulation of VEGF-C expression in lung and colon cancer cells decelerates tumor growth and inhibits metastasis via multiple mechanisms. Oncogene 2012, 31:1389-97.
  • [29]Vignaud JM, Marie B, Klein N, Plenat F, Pech M, Borrelly J, et al.: The role of platelet-derived growth factor production by tumor-associated macrophages in tumor stroma formation in lung cancer. Cancer Res 1994, 54:5455-63.
  • [30]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144:646-74.
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