Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Annexin A7 suppresses lymph node metastasis of hepatocarcinoma cells in a mouse model

Authors: Yanling Jin, Shaoqing Wang, Wenjing Chen, Jun Zhang, Bo Wang, Hongwei Guan, Jianwu Tang

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in China. This study investigated the effects of Annexin A7 (ANXA7) on the inhibition of HCC lymph node metastasis in a mouse model.

Methods

The stable knockup and knockdown of Annexin A7-expressing HCC cells using Annexin A7 cDNA and shRNA vectors, respectively, were injected into a mouse footpad to establish primary and metastatic tumors in mice. On the 14th, 21st, and 28th days after HCC cells inoculation, the mice were sacrificed for inspection of primary and secondary tumors and immunohistochemistry of Annexin A7 expression.

Results

The lymph node metastasis rate of the FANXA7-control group was 77%, and the lymph node metastasis rate of the FANXA7-down group was 100% (p < 0.05). In contrast, the lymph node metastasis rate of the PANXA7-up group was 0% and that of the PANXA7-control group was 36% (p < 0.05). Furthermore, immunohistochemistry experiments revealed that the subcellular localization of Annexin A7 protein in both primary and lymph node-metastasized tumors was mainly in the cytosol. In addition, the expression of the 47 kDa and 51 kDa isoforms of Annexin A7 protein changed during tumor progression.

Conclusion

This study indicated that Annexin A7 expression was able to inhibit HCC lymph node metastasis, whereas knockdown of Annexin A7 expression significantly induced HCC metastasis to local lymph nodes.
Appendix
Available only for authorised users
Literature
1.
Fidler IJ: Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 1990, 50: 6130-6138.PubMed
2.
Li Q, Wu M, Wang H, Xu G, Zhu T, Zhang Y, Liu P, Song A, Gang C, Han Z, Zhou J, Meng L, Lu Y, Wang S, Ma D: Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells. Cancer Lett. 2008, 261: 55-63. 10.1016/j.canlet.2007.11.018.CrossRefPubMed
3.
Li DQ, Hou YF, Wu J, Chen Y, Lu JS, Di GH, Ou ZL, Shen ZZ, Ding J, Shao ZM: Gene expression profile analysis of an isogenic tumour metastasis model reveals a functional role for oncogene AF1Q in breast cancer metastasis. Eur J Cancer. 2006, 42: 3274-3286. 10.1016/j.ejca.2006.07.008.CrossRefPubMed
4.
Jia L, Wang S, Cao J, Zhou H, Wei W, Zhang J: siRNA targeted against matrix metalloproteinase 11 inhibits the metastatic capability of murine hepatocarcinoma cell Hca-F to lymph nodes. Int J Biochem Cell Biol. 2007, 39: 2049-2062. 10.1016/j.biocel.2007.05.023.CrossRefPubMed
5.
Song B, Tang JW, Wang B, Cui XN, Hou L, Sun L, Mao LM, Zhou CH, Du Y, Wang LH, Wang HX, Zheng RS, Sun L: Identify lymphatic metastasis-associated genes in mouse hepatocarcinoma cell lines using gene chip. World J Gastroenterol. 2005, 11: 1463-1472.CrossRefPubMedPubMedCentral
6.
Liu S, Sun MZ, Tang JW, Wang Z, Sun C, Greenaway FT: High-performance liquid chromatography/nano-electrospray ionization tandem mass spectrometry, two-dimensional difference in-gel electrophoresis and gene microarray identification of lymphatic metastasis-associated biomarkers. Rapid Commun Mass Spectrom. 2008, 22: 3172-3178. 10.1002/rcm.3725.CrossRefPubMed
7.
Jin YL, Wang ZQ, Qu H, Wang HX, Ibrahim MM, Zhang J, Huang YH, Wu J, Bai LL, Wang XY, Meng JY, Tang JW: Annexin A7 gene is an important factor in the lymphatic metastasis of tumors. Biomed Pharmacother. 2013, 67: 251-259. 10.1016/j.biopha.2012.11.006.CrossRefPubMed
8.
Hou L, Li Y, Jia YH, Wang B, Xin Y, Ling MY, Lü S: Molecular mechanism about lymphogenous metastasis of hepatocarcinoma cells in mice. World J Gastroenterol. 2001, 7: 532-536.CrossRefPubMedPubMedCentral
9.
Cui XN, Tang JW, Hou L, Song B, Ban LY: Identification of differentially expressed genes in mouse hepatocarcinoma ascites cell line with low potential of lymphogenous metastasis. World J Gastroenterol. 2006, 12: 6893-6897.CrossRefPubMedPubMedCentral
10.
Srivastava M, Bubendorf L, Srikantan V, Fossom L, Nolan L, Glasman M, Leighton X, Fehrle W, Pittaluga S, Raffeld M, Koivisto P, Willi N, Gasser TC, Kononen J, Sauter G, Kallioniemi OP, Srivastava S, Pollard HB: ANX7, a candidate tumor suppressor gene for prostate cancer. Proc Natl Acad Sci U S A. 2001, 98: 4575-4580. 10.1073/pnas.071055798.CrossRefPubMedPubMedCentral
11.
Srivastava M, Atwater I, Glasman M, Leighton X, Goping G, Caohuy H, Miller G, Pichel J, Westphal H, Mears D, Rojas E, Pollard HB: Defects in inositol 1,4,5-trisphosphate receptor expression, Ca(2+) signaling, and insulin secretion in the anx7(+/-) knockout mouse. Proc Natl Acad Sci USA. 1999, 96: 13783-13788. 10.1073/pnas.96.24.13783.CrossRefPubMedPubMedCentral
12.
Srivastava M, Montagna C, Leighton X, Glasman M, Naga S, Eidelman O, Ried T, Pollard HB: Haploinsufficiency of Anx7 tumor suppressor gene and consequent genomic instability promotes tumorigenesis in the Anx7(+/-) mouse. Proc Natl Acad Sci U S A. 2003, 100: 14287-14292. 10.1073/pnas.2235927100.CrossRefPubMedPubMedCentral
13.
Srivastava M, Torosyan Y, Raffeld M, Eidelman O, Pollard HB, Bubendorf L: ANXA7 expression represents hormone-relevant tumor suppression in different cancers. Int J Cancer. 2007, 121: 2628-2636. 10.1002/ijc.23008.CrossRefPubMed
14.
Torosyan Y, Simakova O, Naga S, Mezhevaya K, Leighton X, Diaz J, Huang W, Pollard H, Srivastava M: Annexin-A7 protects normal prostate cells and induces distinct patterns of RB-associated cytotoxicity in androgen-sensitive and -resistant prostate cancer cells. Int J Cancer. 2009, 125: 2528-2539. 10.1002/ijc.24592.CrossRefPubMed
15.
Leighton X, Srikantan V, Pollard HB, Sukumar S, Srivastava M: Significant allelic loss of ANX7 region (10q21) in hormone receptor negative breast carcinomas. Cancer Lett. 2004, 210: 239-244. 10.1016/j.canlet.2004.01.018.CrossRefPubMed
16.
Sun MZ, Liu S, Tang J, Wang Z, Gong X, Sun C, Greenaway F: Proteomics analysis of two mice hepatocarcinoma ascites syngeneic cell lines with high and low lymph node metastasis rates provide potential protein markers for tumor malignancy attributes to lymphatic metastasis. Proteomics. 2009, 9: 3285-3302. 10.1002/pmic.200701002.CrossRefPubMed
17.
Qazi AS, Sun M, Huang Y, Wei Y, Tang J: Subcellular proteomics: determination of specific location and expression levels of lymphatic metastasis associated proteins in hepatocellular carcinoma by subcellular fractionation. Biomed Pharmacother. 2011, 65: 407-416. 10.1016/j.biopha.2011.04.028.CrossRefPubMed
18.
Ibrahim MM, Sun MZ, Huang Y, Jun M, Jin Y, Yue D, Jiasheng W, Zhang J, Qazi AS, Sagoe K, Tang J: Down-regulation of ANXA7 decreases metastatic potential of human hepatocellular carcinoma cells in vitro. Biomed Pharmacother. 2013, 67: 285-291. 10.1016/j.biopha.2013.02.005.CrossRefPubMed
19.
Jin Y, Mao J, Wang H, Hou Z, Ma W, Zhang J, Wang B, Huang Y, Zang S, Tang J, Li L: Enhanced tumorigenesis and lymphatic metastasis of CD133+ hepatocarcinoma ascites syngeneic cell lines mediated by JNK signaling pathway in vitro and in vivo. Biomed Pharmacother. 2013, 67: 337-345. 10.1016/j.biopha.2013.02.006.CrossRefPubMed
20.
Rick M, Ramos Garrido SI, Herr C, Thal DR, Noegel AA, Clemen CS: Nuclear localization of Annexin A7 during murine brain development. BMC Neurosci. 2005, 6: 25-10.1186/1471-2202-6-25.CrossRefPubMedPubMedCentral
21.
Hsu PI, Huang MS, Chen HC, Hsu PN, Lai TC, Wang JL, Lo GH, Lai KH, Tseng CJ, Hsiao M: The significance of ANXA7 expression and its correlation with poor cellular differentiation and enhanced metastatic potential of gastric cancer. J Surg Oncol. 2008, 97: 609-614. 10.1002/jso.21046.CrossRefPubMed
22.
Srivastava M, Bubendorf L, Raffeld M, Bucher C, Torhorst J, Sauter G, Olsen C, Kallioniemi OP, Eidelman O, Pollard HB: Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients. Clin Cancer Res. 2004, 10: 2344-2350. 10.1158/1078-0432.CCR-03-0278.CrossRefPubMed
23.
Smitherman AB, Mohler JL, Maygarden SJ, Ornstein DK: Expression of annexin I, II and VII proteins in androgen stimulated and recurrent prostate cancer. J Urol. 2004, 171: 916-920. 10.1097/01.ju.0000104674.70170.cd.CrossRefPubMed
24.
Yu F, Finley RL, Raz A, Kim HR: Galectin-3 translocates to the perinuclear membranes and inhibits cytochrome c release from the mitochondria. A role for synexin in galectin-3 translocation. J Biol Chem. 2002, 277: 15819-15827. 10.1074/jbc.M200154200.CrossRefPubMed
25.
Nir S, Stutzin A, Pollard HB: Effect of synexin on aggregation and fusion of chromaffin granule ghosts at pH 6. Biochim Biophys Acta. 1987, 903: 309-318. 10.1016/0005-2736(87)90221-5.CrossRefPubMed
26.
Pollard HB, Rojas E, Burns AL: Synexin (annexin VII) and membrane fusion during the process of exocytotic secretion. Prog Brain Res. 1992, 92: 247-255.CrossRefPubMed
27.
Palmer RE, Lee SB, Wong JC, Reynolds PA, Zhang H, Truong V, Oliner JD, Gerald WL, Haber DA: Induction of BAIAP3 by the EWS-WT1 chimeric fusion implicates regulated exocytosis in tumorigenesis. Cancer Cell. 2002, 2: 497-505. 10.1016/S1535-6108(02)00205-2.CrossRefPubMed
28.
Addya S, Shiroto K, Turoczi T, Zhan L, Kaga S, Fukuda S, Surrey S, Duan LJ, Fong GH, Yamamoto F, Maulik N: Ischemic preconditioning-mediated cardioprotection is disrupted in heterozygous Flt-1 (VEGFR-1) knockout mice. J Mol Cell Cardiol. 2005, 38: 345-351. 10.1016/j.yjmcc.2004.11.033.CrossRefPubMed
29.
Ji H, Moritz RL, Kim YS, Zhu HJ, Simpson RJ: Analysis of Ras-induced oncogenic transformation of NIH-3 T3 cells using differential-display 2-DE proteomics. Electrophoresis. 2007, 28: 1997-2008. 10.1002/elps.200700009.CrossRefPubMed
30.
Clemen CS, Herr C, Lie AA, Noegel AA, Schröder R: Annexin VII: an astroglial protein exhibiting a Ca2 + -dependent subcellular distribution. Neuroreport. 2001, 12: 1139-1144. 10.1097/00001756-200105080-00018.CrossRefPubMed
31.
Hoyer DP, Grönke S, Frank KF, Addicks K, Wettschureck N, Offermanns S, Erdmann E, Reuter H: Diabetes-related defects in sarcoplasmic Ca2+ release are prevented by inactivation of G(alpha)11 and G(alpha)q in murine cardiomyocytes. Mol Cell Biochem. 2010, 341: 235-244. 10.1007/s11010-010-0454-1.CrossRefPubMed
32.
Clemen CS, Hofmann A, Zamparelli C, Noegel AA: Expression and localisation of annexin VII (synexin) isoforms in differentiating myoblasts. J Muscle Res Cell Motil. 1999, 20: 669-679. 10.1023/A:1005524623337.CrossRefPubMed
33.
Herr C, Clemen CS, Lehnert G, Kutschkow R, Picker SM, Gathof BS, Zamparelli C, Schleicher M, Noegel AA: Function, expression and localization of annexin A7 in platelets and red blood cells: insights derived from an annexin A7 mutant mouse. BMC Biochem. 2003, 4: 8-10.1186/1471-2091-4-8.CrossRefPubMedPubMedCentral
34.
Magendzo K, Shirvan A, Cultraro C, Srivastava M, Pollard HB, Burns AL: Alternative splicing of human synexin mRNA in brain, cardiac, and skeletal muscle alters the unique N-terminal domain. J Biol Chem. 1991, 266: 3228-3232.PubMed
35.
Selbert S, Fischer P, Pongratz D, Stewart M, Noegel AA: Expression and localization of annexin VII (synexin) in muscle cells. J Cell Sci. 1995, 108: 85-95.PubMed
Metadata
Title
Annexin A7 suppresses lymph node metastasis of hepatocarcinoma cells in a mouse model
Authors
Yanling Jin
Shaoqing Wang
Wenjing Chen
Jun Zhang
Bo Wang
Hongwei Guan
Jianwu Tang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-522

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue

Research article

Resveratrol abrogates the Temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the Temozolomide-induced senescence in glioma cells

Research article

Multicentric and multifocal versusunifocal breast cancer: differences in the expression of E-cadherin suggest differences in tumor biology

Research article

EphB4 as a therapeutic target in mesothelioma

Research article

Heparan sulfate mediates trastuzumab effect in breast cancer cells

Research article

NOTCH1 mutations influence survival in chronic lymphocytic leukemia patients

Research article

CD26 Expression on T-Anaplastic Large Cell Lymphoma (ALCL) Line Karpas 299 is associated with increased expression of Versican and MT1-MMP and enhanced adhesion
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits