Abstract
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.
References
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.
Shah MA, Ajani JA. Gastric cancer—an enigmatic and heterogeneous disease. JAMA. 2010;303:1753–4. doi:10.1001/jama.2010.553.
Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62.
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.
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.
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.
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.
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.
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.
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.
Guo T, Fan L, Ng WH, et al. Multidimensional identification of tissue biomarkers of gastric cancer. J Proteome Res. 2012;. doi:10.1021/pr300212g.
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.
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.
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.
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.
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.
Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev. 2002;82:331–71. doi:10.1152/physrev.00030.2001.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Acknowledgments
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.
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Leal, M.F., Calcagno, D.Q., Chung, J. et al. Deregulated expression of annexin-A2 and galectin-3 is associated with metastasis in gastric cancer patients. Clin Exp Med 15, 415–420 (2015). https://doi.org/10.1007/s10238-014-0299-0
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DOI: https://doi.org/10.1007/s10238-014-0299-0