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Down-regulation of plasma membranous Annexin A1 protein expression in premalignant and malignant lesions of the oral cavity: correlation with epithelial differentiation

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Abstract

Purpose

To determine the potential involvement of ANXA1 in oral squamous-cell carcinoma (OSCC), we evaluated the ANXA1 protein expression in oral premalignant lesions (OPLs) and OSCCs and correlated the results with clinicopathologic variables.

Methods

Matched normal and tumour specimens of 44 primary OSCCs and 28 OPLs were analyzed for ANXA1 subcellular localization and protein expression level by immunohistochemistry (IHC). Correlations between ANXA1-IHC staining scores of OSCCs and clinicopathologic features were evaluated by Fisher’s exact test.

Results

Markedly down-regulation of ANXA1 protein expression was identified on the plasma membrane of epithelial cells in OSCCs (P < 0.001) and OPLs (P = 0.001) compared with normal counterparts. Moreover, loss of plasma membranous ANXA1 expression was significantly correlated with the poorly differentiated status of OSCC cells (P = 0.012).

Conclusions

Our findings suggest that loss of ANXA1 is frequent and early event during oral carcinogenesis and that ANXA1 could contribute to maintaining epithelial differentiation in OSCC.

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References

  • Alldridge LC, Bryant CE (2003) Annexin 1 regulates cell proliferation by disruption of cell morphology and inhibition of cyclin D1 expression through sustained activation of the ERK1/2 MAPK signal. Exp Cell Res 290:93–107. doi:10.1016/S0014-4827(03)00310-0

    Article  PubMed  CAS  Google Scholar 

  • Bai XF, Ni XG, Zhao P, Liu SM, Wang HX, Guo B, Zhou LP, Liu F, Zhang JS, Wang K, Xie YQ, Shao YF, Zhao XH (2004) Overexpression of annexin 1 in pancreatic cancer and its clinical significance. World J Gastroenterol 10:1466–1470

    PubMed  CAS  Google Scholar 

  • Bilalovic N, Sandstad B, Golouh R, Nesland JM, Selak I, Torlakovic EE (2004) CD10 protein expression in tumor and stromal cells of malignant melanoma is associated with tumor progression. Mod Pathol 17:1251–1258. doi:10.1038/modpathol.3800174

    Article  PubMed  CAS  Google Scholar 

  • de Coupade C, Gillet R, Bennoun M, Briand P, Russo-Marie F, Solito E (2000) Annexin 1 expression and phosphorylation are upregulated during liver regeneration and transformation in antithrombin III SV40 T large antigen transgenic mice. Hepatology 31:371–380. doi:10.1002/hep.510310217

    Article  PubMed  Google Scholar 

  • Gerke V, Moss SE (2002) Annexins: from structure to function. Physiol Rev 82:331–371

    PubMed  CAS  Google Scholar 

  • Goulding NJ, Godolphin JL, Sampson MB, Maddison PJ, Flower RJ (1990) Hydrocortisone induces lipocortin 1 production by peripheral blood mononuclear cells in vivo in man. Biochem Soc Trans 18:306–307

    PubMed  CAS  Google Scholar 

  • Guzmán-Aránguez A, Olmo N, Turnay J, Lecona E, Pérez-Ramos P, López de Silanes I, Lizarbe MA (2005) Differentiation of human colon adenocarcinoma cells alters the expression and intracellular localization of annexins A1, A2, and A5. J Cell Biochem 94:178–193. doi:10.1002/jcb.20293

    Article  PubMed  Google Scholar 

  • Horton P, Park KJ, Obayashi T, Fujita N, Harada H, Adams-Collier CJ, Nakai K (2007) WoLF PSORT: protein localization predictor. Nucleic Acids Res 35:585–587. doi:10.1093/nar/gkm259

    Article  Google Scholar 

  • Hu N, Flaig MJ, Su H, Shou JZ, Roth MJ, Li WJ, Wang C, Goldstein AM, Li G, Emmert-Buck MR, Taylor PR (2004) Comprehensive characterization of annexin I alterations in esophageal squamous-cell carcinoma. Clin Cancer Res 10:6013–6022. doi:10.1158/1078-0432.CCR-04-0317

    Article  PubMed  CAS  Google Scholar 

  • Huo XF, Zhang JW (2005) Annexin1 regulates the erythroid differentiation through ERK signaling pathway. Biochem Biophys Res Commun 331:1346–1352. doi:10.1016/j.bbrc.2005.04.049

    Article  PubMed  CAS  Google Scholar 

  • Johnson MD, Kamso-Pratt J, Pepinsky RB, Whetsell WO Jr (1989) Lipocortin-1 immunoreactivity in central and peripheral nervous system glial tumors. Hum Pathol 20:772–776. doi:10.1016/0046-8177(89)90071-3

    Article  PubMed  CAS  Google Scholar 

  • Kang SA, Cho YJ, Moon HB, Na DS (1996) Translocation of lipocortin (annexin) 1 to the membrane of U937 cells induced by phorbol ester, but not by dexamethasone. Br J Pharmacol 117:1780–1784

    PubMed  CAS  Google Scholar 

  • Kang JS, Calvo BF, Maygarden SJ, Caskey LS, Mohler JL, Ornstein DK (2002) Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer. Clin Cancer Res 8:117–123

    PubMed  CAS  Google Scholar 

  • Koike H, Uzawa K, Nakashima D, Shimada K, Kato Y, Higo M, Kouzu Y, Endo Y, Kasamatsu A, Tanzawa H (2005) Identification of differentially expressed proteins in oral squamous cell carcinoma using a global proteomic approach. Int J Oncol 27:59–67

    PubMed  CAS  Google Scholar 

  • La Vecchia C, Lucchini F, Negri E, Levi F (2004) Trends in oral cancer mortality in Europe. Oral Oncol 40:433–439. doi:10.1016/j.oraloncology.2003.09.013

    Article  PubMed  Google Scholar 

  • Lim LH, Pervaiz S (2007) Annexin 1: the new face of an old molecule. FASEB J 21:968–975. doi:10.1096/fj.06-7464rev

    Article  PubMed  CAS  Google Scholar 

  • Lin CY, Jeng YM, Chou HY, Hsu HC, Yuan RH, Chiang CP, Kuo MY (2008) Nuclear localization of annexin A1 is a prognostic factor in oral squamous cell carcinoma. J Surg Oncol 97:544–550. doi:10.1002/jso.20992

    Article  PubMed  CAS  Google Scholar 

  • Masaki T, Tokuda M, Ohnishi M, Watanabe S, Fujimura T, Miyamoto K, Itano T, Matsui H, Arima K, Shirai M, Maeba T, Sogawa K, Konishi R, Taniguchi K, Hatanaka Y, Hatase O, Nishioka M (1996) Enhanced expression of the protein kinase substrate annexin in human hepatocellular carcinoma. Hepatology 24:72–81

    PubMed  CAS  Google Scholar 

  • McCarty KS Jr, Szabo E, Flowers JL, Cox EB, Leight GS, Miller L, Konrath J, Soper JT, Budwit DA, Creasman WT, Seigler HF, McCarty KS Sr (1986) Use of monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res 46:4244–4248

    Google Scholar 

  • Paweletz CP, Ornstein DK, Roth MJ, Bichsel VE, Gillespie JW, Calvert VS, Vocke CD, Hewitt SM, Duray PH, Herring J, Wang QH, Hu N, Linehan WM, Taylor PR, Liotta LA, Emmert-Buck MR, Petricoin EF 3rd (2000) Loss of annexin 1 correlates with early onset of tumorigenesis in esophageal and prostate carcinoma. Cancer Res 60:6293–6297

    PubMed  CAS  Google Scholar 

  • Pedrero JMG, Fernandez MP, Morgan RO, Herrero Zapatero A, Gonzalez MV, Suarez Nieto C, Rodrigo JP (2004) Annexin A1 down-regulation in head and neck cancer is associated with epithelial differentiation status. Am J Pathol 164:73–79

    CAS  Google Scholar 

  • Pepinsky RB (1991) Phosphorylation of lipocortin-1 by the epidermal growth factor receptor. Methods Enzymol 198:260–272. doi:10.1016/0076-6879(91)98027-4

    Article  PubMed  CAS  Google Scholar 

  • Rodrigo JP, Garcia-Pedrero JM, Fernandez MP, Morgan RO, Suárez C, Herrero A (2005) Annexin A1 expression in nasopharyngeal carcinoma correlates with squamous differentiation. Am J Rhinol 19:483–487

    PubMed  Google Scholar 

  • Shen D, Nooraie F, Elshimali Y, Lonsberry V, He J, Bose S, Chia D, Seligson D, Chang HR, Goodglick L (2006) Decreased expression of annexin A1 is correlated with breast cancer development and progression as determined by a tissue microarray analysis. Hum Pathol 37:1583–1591. doi:10.1016/j.humpath.2006.06.001

    Article  PubMed  CAS  Google Scholar 

  • Sinha P, Hutter G, Kottgen E, Dietel M, Schadendorf D, Lage H (1998) Increased expression of annexin I and thioredoxin detected by two-dimensional gel electrophoresis of drug resistant human stomach cancer cells. J Biochem Biophys Methods 37:105–116. doi:10.1016/S0165-022X(98)00020-7

    Article  PubMed  CAS  Google Scholar 

  • Solito E, Nuti S, Parente L (1994) Dexamethasone-induced translocation of lipocortin (annexin) 1 to the cell membrane of U-937 cells. Br J Pharmacol 112:347–348

    PubMed  CAS  Google Scholar 

  • Solito E, de Coupade C, Parente L, Flower RJ, Russo-Marie F (1998) Human annexin 1 is highly expressed during the differentiation of the epithelial cell line A 549: involvement of nuclear factor interleukin 6 in phorbol ester induction of annexin 1. Cell Growth Differ 9:327–336

    PubMed  CAS  Google Scholar 

  • Solito E, Kamal A, Russo-Marie F, Buckingham JC, Marullo S, Perretti M (2003) A novel calcium-dependent proapoptotic effect of annexin 1 on human neutrophils. FASEB J 17:1544–1546

    PubMed  CAS  Google Scholar 

  • Sudbo J, Reith A (2005) The evolution of predictive oncology and molecular-based therapy for oral cancer prevention. Int J Cancer 115:339–345. doi:10.1002/ijc.20896

    Article  PubMed  CAS  Google Scholar 

  • Violette SM, King I, Browning JL, Pepinsky RB, Wallner BP, Sartorelli AC (1990) Role of lipocortin I in the glucocorticoid induction of the terminal differentiation of a human squamous carcinoma. J Cell Physiol 142:70–77. doi:10.1002/jcp.1041420110

    Article  PubMed  CAS  Google Scholar 

  • Vishwanatha JK, Salazar E, Gopalakrishnan VK (2004) Absence of annexin I expression in B-cell non-Hodgkin’s lymphomas and cell lines. BMC Cancer 4:8. doi:10.1186/1471-2407-4-8

    Article  PubMed  Google Scholar 

  • Wang KL, Wu TT, Resetkova E, Wang H, Correa AM, Hofstetter WL, Swisher SG, Ajani JA, Rashid A, Hamilton SR, Albarracin CT (2006) Expression of annexin A1 in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome. Clin Cancer Res 12:4598–4604. doi:10.1158/1078-0432.CCR-06-0483

    Article  PubMed  CAS  Google Scholar 

  • Xia SH, Hu LP, Hu H, Ying WT, Xu X, Cai Y, Han YL, Chen BS, Wei F, Qian XH, Cai YY, Shen Y, Wu M, Wang MR (2002) Three isoforms of annexin I are preferentially expressed in normal esophageal epithelia but down-regulated in esophageal squamous cell carcinomas. Oncogene 21:6641–6648. doi:10.1038/sj.onc.1205818

    Article  PubMed  CAS  Google Scholar 

  • Yang M, Liu W, Wang CY, Liu T, Zhou F, Tao J, Wang Y, Li MT (2006) Proteomic analysis of differential protein expression in early process of pancreatic regeneration in pancreatectomized rats. Acta Pharmacol Sin 27:568–578. doi:10.1111/j.1745-7254.2006.00317.x

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was partly supported by a Grant-in-Aid Scientific Research (No. 20791492) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Global COE Program (Global Center for Education and Research in Immune System Regulation and Treatment), MEXT, Japan.

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Authors and Affiliations

  1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Hitomi Nomura, Katsuhiro Uzawa, Yukio Yamano, Kazuaki Fushimi, Dai Nakashima, Yukinao Kouzu, Atsushi Kasamatsu, Katsunori Ogawara, Masashi Shiiba & Hideki Tanzawa

  2. Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Katsuhiro Uzawa, Hiroki Bukawa, Hidetaka Yokoe & Hideki Tanzawa

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  1. Hitomi Nomura
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  2. Katsuhiro Uzawa
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Correspondence to Hideki Tanzawa.

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Nomura, H., Uzawa, K., Yamano, Y. et al. Down-regulation of plasma membranous Annexin A1 protein expression in premalignant and malignant lesions of the oral cavity: correlation with epithelial differentiation. J Cancer Res Clin Oncol 135, 943–949 (2009). https://doi.org/10.1007/s00432-008-0530-z

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  • DOI: https://doi.org/10.1007/s00432-008-0530-z

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