Clinical and Experimental Medicine

, Volume 15, Issue 3, pp 415–420 | Cite as

Deregulated expression of annexin-A2 and galectin-3 is associated with metastasis in gastric cancer patients

  • Mariana Ferreira LealEmail author
  • Danielle Queiroz Calcagno
  • Janete Chung
  • Vanessa Morais de Freitas
  • Samia Demachki
  • Paulo Pimentel Assumpção
  • Roger Chammas
  • Rommel Rodríguez Burbano
  • Marília Cardoso Smith
Letter to the Editor


Gastric cancer (GC) is the second highest cause of cancer mortality worldwide. However, nowadays, most of the studies aiming to understand the gastric carcinogenesis analyzed tumors of individuals from Asian population and, thus, may not reflect the distinct biological and clinical behaviors among GC processes. Since several membrane proteins have been implicated in carcinogenesis, we aimed to evaluate ANXA2 and GAL3 role in gastric tumors and GC cell lines of individuals from northern Brazil. The cellular localization of ANXA2 and GAL3 in the GC cell lines was evaluated by immunofluorescence. Gene expression was evaluated by real-time reverse-transcription PCR and protein expression by Western blot in gastric adenocarcinomas and non-neoplastic gastric samples, as well as in GC cell lines. ANXA2 and GAL3 were presented as dots in the plasma membrane and cytoplasm in ACP02 and ACP03 cell lines. ANXA2 mRNA expression was up-regulated in 32.14 % of gastric tumors compared to non-neoplastic tissues. ANXA2 up-regulation was associated with the metastasis process in vivo and with cell line invasive behavior. GAL3 protein expression was at least 1.5-fold reduced in 50 % of gastric tumors. The reduced GAL3 expression was associated with the presence of distant metastasis and with a higher invasive phenotype in vitro. Our study shows that ANXA2 and GAL3 deregulated expression was associated with an invasive phenotype in GC cell lines and may contribute to metastasis in GC patients. Therefore, these proteins may have potential prognostic relevance for GC of individuals from northern Brazil.


Membrane proteins Proteomic Gastric cancer Annexin 2 Galectin-3 



This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; RC, MACS and RRB) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; MFL, JC and DQC) as grants and fellowship awards. We acknowledge the Mass Spectrometry Laboratory at Brazilian Biosciences National Laboratory, CNPEM-ABTLuS, Campinas, Brazil and Dr. Adriana F. Paes Leme and technicians for their assistance with the mass spectrometric analyses.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10238_2014_299_MOESM1_ESM.doc (455 kb)
Supplementary material 1 (DOC 455 kb)
10238_2014_299_MOESM2_ESM.xls (456 kb)
Supplementary material 2 (XLS 456 kb)


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Shah MA, Ajani JA. Gastric cancer—an enigmatic and heterogeneous disease. JAMA. 2010;303:1753–4. doi: 10.1001/jama.2010.553.CrossRefPubMedGoogle Scholar
  3. 3.
    Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Adam PJ, Boyd R, Tyson KL, et al. Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer. J Biol Chem. 2003;278:6482–9. doi: 10.1074/jbc.M210184200.CrossRefPubMedGoogle Scholar
  5. 5.
    Leal MF, Chung J, Calcagno DQ, Assumpcao PP, et al. Differential proteomic analysis of noncardia gastric cancer from individuals of northern Brazil. PLoS One. 2012;7:e42255. doi: 10.1371/journal.pone.0042255PONE-D-11-08927.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Batista dos Santos SE, Rodrigues JD, Ribeiro-dos-Santos AK, Zago MA. Differential contribution of indigenous men and women to the formation of an urban population in the Amazon region as revealed by mtDNA and Y-DNA. Am J Phys Anthropol. 1999;109:175–80. doi: 10.1002/(SICI)1096-8644(199906)109:2<175::AID-AJPA3>3.0.CO;2-%23.CrossRefPubMedGoogle Scholar
  7. 7.
    Leal MF, Martins do Nascimento JL, da Silva CE, et al. Establishment and conventional cytogenetic characterization of three gastric cancer cell lines. Cancer Genet Cytogenet. 2009;195:85–91. doi: 10.1016/j.cancergencyto.2009.04.020.CrossRefPubMedGoogle Scholar
  8. 8.
    Leal MF, Calcagno DQ, Costa JFFB, et al. MYC, TP53, and chromosome 17 copy-number alterations in multiple gastric cancer cell lines and in their parental primary tumors. J Biomed Biotechnol. 2011;. doi: 10.1155/2011/631268.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Calcagno DQ, Freitas VM, Leal MF, et al. MYC, FBXW7 and TP53 copy number variation and expression in gastric cancer. BMC Gastroenterol. 2013;13:141. doi: 10.1186/1471-230X-13-141.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    da Costa Jde F, Leal MF, Silva TC, et al. Experimental gastric carcinogenesis in Cebus apella nonhuman primates. PLoS One. 2011;6:e21988. doi: 10.1371/journal.pone.0021988PONE-D-11-03343.CrossRefGoogle Scholar
  11. 11.
    Guo T, Fan L, Ng WH, et al. Multidimensional identification of tissue biomarkers of gastric cancer. J Proteome Res. 2012;. doi: 10.1021/pr300212g.Google Scholar
  12. 12.
    Hofmann A, Gerrits B, Schmidt A, et al. Proteomic cell surface phenotyping of differentiating acute myeloid leukemia cells. Blood. 2010;116:e26–34. doi: 10.1182/blood-2010-02-271270.CrossRefPubMedGoogle Scholar
  13. 13.
    Ponten F, Jirstrom K, Uhlen M. The human protein atlas—a tool for pathology. J Pathol. 2008;216:387–93. doi: 10.1002/path.2440.CrossRefPubMedGoogle Scholar
  14. 14.
    Leal MF, Mazzotti TK, Calcagno DQ, et al. Deregulated expression of Nucleophosmin 1 in gastric cancer and its clinicopathological implications. BMC Gastroenterol. 2014;14:9. doi: 10.1186/1471-230X-14-9.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Leal MF, Calcagno DQ, Demachki S, et al. Clinical implication of 14-3-3 epsilon expression in gastric cancer. World J Gastroenterol. 2012;18:1531–7.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Emoto K, Sawada H, Yamada Y, et al. Annexin II overexpression is correlated with poor prognosis in human gastric carcinoma. Anticancer Res. 2001;21:1339–45.PubMedGoogle Scholar
  17. 17.
    Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev. 2002;82:331–71. doi: 10.1152/physrev.00030.2001.CrossRefPubMedGoogle Scholar
  18. 18.
    Filipenko NR, Waisman DM. The C terminus of annexin II mediates binding to F-actin. J Biol Chem. 2001;276:5310–5. doi: 10.1074/jbc.M009710200.CrossRefPubMedGoogle Scholar
  19. 19.
    Hansen MD, Ehrlich JS, Nelson WJ. Molecular mechanism for orienting membrane and actin dynamics to nascent cell–cell contacts in epithelial cells. J Biol Chem. 2002;277:45371–6. doi: 10.1074/jbc.M207747200.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Babbin BA, Parkos CA, Mandell KJ, et al. Annexin 2 regulates intestinal epithelial cell spreading and wound closure through Rho-related signaling. Am J Pathol. 2007;170:951–66. doi: 10.2353/ajpath.2007.060647.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Dong WG, Yu QF, Xu Y, Fan LF. Li-cadherin is inversely correlated with galectin-3 expression in gastric cancer. Dig Dis Sci. 2008;53:1811–7. doi: 10.1007/s10620-007-0080-2.CrossRefPubMedGoogle Scholar
  22. 22.
    Miyazaki J, Hokari R, Kato S, et al. Increased expression of galectin-3 in primary gastric cancer and the metastatic lymph nodes. Oncol Rep. 2002;9:1307–12.PubMedGoogle Scholar
  23. 23.
    Baldus SE, Zirbes TK, Weingarten M, et al. Increased galectin-3 expression in gastric cancer: correlations with histopathological subtypes, galactosylated antigens and tumor cell proliferation. Tumour Biol. 2000;21:258–66.CrossRefPubMedGoogle Scholar
  24. 24.
    Okada K, Shimura T, Suehiro T, Mochiki E, Kuwano H. Reduced galectin-3 expression is an indicator of unfavorable prognosis in gastric cancer. Anticancer Res. 2006;26:1369–76.PubMedGoogle Scholar
  25. 25.
    Ellerhorst J, Troncoso P, Xu XC, Lee J, Lotan R. Galectin-1 and galectin-3 expression in human prostate tissue and prostate cancer. Urol Res. 1999;27:362–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Pacis RA, Pilat MJ, Pienta KJ, et al. Decreased galectin-3 expression in prostate cancer. Prostate. 2000;44:118–23. doi: 10.1002/1097-0045(20000701)44:2<118:AID-PROS4>3.0.CO;2-U.CrossRefPubMedGoogle Scholar
  27. 27.
    van den Brule FA, Berchuck A, Bast RC, et al. Differential expression of the 67-kD laminin receptor and 31-kD human laminin-binding protein in human ovarian carcinomas. Eur J Cancer. 1994;30A:1096–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Lotz MM, Andrews CW Jr, Korzelius CA, et al. Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma. Proc Natl Acad Sci USA. 1993;90:3466–70.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Choufani G, Nagy N, Saussez S, et al. The levels of expression of galectin-1, galectin-3, and the Thomsen–Friedenreich antigen and their binding sites decrease as clinical aggressiveness increases in head and neck cancers. Cancer. 1999;86:2353–63.CrossRefPubMedGoogle Scholar
  30. 30.
    Castronovo V, Van Den Brule FA, Jackers P, et al. Decreased expression of galectin-3 is associated with progression of human breast cancer. J Pathol. 1996;179:43–8. doi: 10.1002/(SICI)1096-9896(199605)179:1<43:AID-PATH541>3.0.CO;2-N.CrossRefPubMedGoogle Scholar
  31. 31.
    de Oliveira JT, de Matos AJ, Gomes J, et al. Coordinated expression of galectin-3 and galectin-3-binding sites in malignant mammary tumors: implications for tumor metastasis. Glycobiology. 2010;20:1341–52. doi: 10.1093/glycob/cwq103.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  • Mariana Ferreira Leal
    • 1
    • 2
    Email author
  • Danielle Queiroz Calcagno
    • 1
    • 5
  • Janete Chung
    • 3
  • Vanessa Morais de Freitas
    • 4
  • Samia Demachki
    • 5
  • Paulo Pimentel Assumpção
    • 5
  • Roger Chammas
    • 6
    • 7
  • Rommel Rodríguez Burbano
    • 8
  • Marília Cardoso Smith
    • 1
  1. 1.Disciplina de Genética, Departamento de Morfologia e GenéticaUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Departamento de Ortopedia e TraumatologiaUniversidade Federal de São PauloSão PauloBrazil
  3. 3.Departamento de Microbiologia, Imunologia e ParasitologiaUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Laboratório de Biologia da Matriz Extracelular, Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências BiomédicasUniversidade de São PauloSão PauloBrazil
  5. 5.Núcleo de Pesquisa em Oncologia, Hospital Universitário João de Barros BarretoUniversidade Federal do ParáBelémBrazil
  6. 6.Laboratório de Oncologia Experimental, Departamento de Radiologia, Faculdade de MedicinaUniversidade de São PauloSão PauloBrazil
  7. 7.Centro de Investigação Translacional em OncologiaInstituto do Câncer do Estado de São PauloSão PauloBrazil
  8. 8.Laboratório de Citogenética Humana, Instituto de Ciências BiológicasUniversidade Federal do ParáBelémBrazil

Personalised recommendations