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YU Tianhong, Siva Bharath MERUGU, Hema NEGI, SUN Songxuan, DING Yunhe, WU Zhenghua, LI Dawei. AGR2-blocking antibody 18A4 inhibits cellular tumorigenic properties induced by extracellular AGR2[J]. Journal of China Pharmaceutical University, 2018, 49(2): 238-246. DOI: 10.11665/j.issn.1000-5048.20180215
Citation: YU Tianhong, Siva Bharath MERUGU, Hema NEGI, SUN Songxuan, DING Yunhe, WU Zhenghua, LI Dawei. AGR2-blocking antibody 18A4 inhibits cellular tumorigenic properties induced by extracellular AGR2[J]. Journal of China Pharmaceutical University, 2018, 49(2): 238-246. DOI: 10.11665/j.issn.1000-5048.20180215

AGR2-blocking antibody 18A4 inhibits cellular tumorigenic properties induced by extracellular AGR2

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  • This study was to evaluate the cellular inhibition effects induced by anti-AGR2 monoclonal antibody 18A4 in two AGR2-negative melanoma cells, A375 and B16-F10, treated with external oncoprotein AGR2. MTT assay and colony formation assay were performed to detect the cell proliferation rate. Flow cytometry analysis was performed to evaluate cell cycle transition. Cell migration rate was analyzed by wound healing assay. Cell morphological changes were detected by phalloidin staining. The expression of p53 was detected by Western blotting and immunofluorescence. Results showed that 18A4 inhibited the AGR2-dependent tumor properties including enhanced proliferation, accelerated cell cycle, increased cell migration and morphological changes of cells. In addition, by Western blot analysis and immunofluorescence, AGR2 blocking antibody 18A4 also restored p53 expression that was repressed by external AGR2 treated by chemotherapeutic drug doxorubicin. These findings suggest that 18A4 is able to inhibit the cellular tumorigenic properties induced by external AGR2 and is a potential drug against fumor.
  • [1]
    Kumar A,Godwin JW,Gates PB,et al.Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate[J].Science,2007,318(5851):772-777.
    [2]
    Zhu Q,Mangukiya HB,Mashausi DS,et al.Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain [J].FEBS J,2017,284(17):2856-2869.
    [3]
    Wodziak D,Dong A,Basin MF,et al.Anterior gradient 2(AGR2)induced epidermal growth factor receptor(EGFR)signaling is essential for murine pancreatitis-associated tissue regeneration[J].PLoS One,2016,11(10):e0164968.
    [4]
    Liu D, Rudland PS, Sibson DR, et al. Human homologue of cement gland protein,a novel metastasis inducer associated with breast carcinomas[J].Cancer Res,2005,65(9):3796-3805.
    [5]
    Ramachandran V,Arumugam T,Wang H,et al.Anterior gradient 2 is expressed and secreted during the development of pancreatic cancer and promotes cancer cell survival[J].Cancer Res,2008,68(19):7811-7818.
    [6]
    Zhang JS,Gong A,Cheville JC,et al.AGR2,an androgen-inducible secretory protein overexpressed in prostate cancer[J].Genes Chromosomes Cancer,2005,43(3):249-259.
    [7]
    Fritzsche FR,Dahl E,Dankof A,et al.Expression of AGR2 in non small cell lung cancer[J].Histol Histopathol,2007,22(7):703-708.
    [8]
    Park K,Chung YJ,So H,et al.AGR2,a mucinous ovarian cancer marker,promotes cell proliferation and migration[J].Exp Mol Med,2011,43(2):91-100.
    [9]
    Chevet E,Fessart D,Delom F,et al.Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development[J].Oncogene,2013,32(20):2499-509.
    [10]
    Brychtova V,Vojtesek B,Hrstka R.Anterior gradient 2:a novel player in tumor cell biology[J].Cancer Lett,2011,304(1):1-7.
    [11]
    Li Z,Zhu Q,Hu L,et al.Anterior gradient 2 is a binding stabilizer of hypoxia inducible factor-1alpha that enhances CoCl2-induced doxorubicin resistance in breast cancer cells[J].Cancer Sci,2015,106(8):1041-1049.
    [12]
    Li Z, Zhu Q, Chen H, et al. Binding of anterior gradient 2 and estrogen receptor-alpha:dual critical roles in enhancing fulvestrant resistance and IGF-1-induced tumorigenesis of breast cancer[J].Cancer Lett,2016,377(1):32-43.
    [13]
    Bu H,Bormann S,Schafer G,et al.The anterior gradient 2(AGR2)gene is overexpressed in prostate cancer and may be useful as a urine sediment marker for prostate cancer detection[J].Prostate,2011,71(6):575-587.
    [14]
    Edgell TA,Barraclough DL,Rajic A,et al.Increased plasma concentrations of anterior gradient 2 protein are positively associated with ovarian cancer[J].Clin Sci(Lond),2010,118(12):717-725.
    [15]
    Vitello EA, Quek SI, Kincaid H, et al. Cancer-secreted AGR2 induces programmed cell death in normal cells[J].Oncotarget,2016,7(31):49425-49434.
    [16]
    Fessart D,Domblides C,Avril T,et al.Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties[J].Elife,2016,5:e13887.
    [17]
    Guo H,Zhu Q,Yu X,et al.Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization[J].Oncogene,2017,36(36):5098-5109.
    [18]
    Wu ZH,Zhu Q,Gao GW,et al.Preparation,characterization and potential application of monoclonal antibody 18A4 against AGR2[J].Chin J Cell Mol Immunol(细胞与分子免疫学杂志),2010,26(1):49-51.
    [19]
    李坤.AGR2单克隆抗体18A4抑制乳腺癌细胞的生长和迁移[D].上海:上海交通大学,2011.
    [20]
    Guo H,Chen H,Zhu Q,et al.A humanized monoclonal antibody targeting secreted anterior gradient 2 effectively inhibits the xenograft tumor growth[J].Biochem Biophys Res Commun,2016,475(1):57-63.
    [21]
    Li K.Monoclonal 18A4 against AGR2 inhibit human breast adenocarcinoma cell growth and migration[D].Shanghai:Shanghai Jiao Tong University,2011.
    [22]
    Vanderlaag KE,Hudak S,Bald L,et al.Anterior gradient-2 plays a critical role in breast cancer cell growth and survival by modulating cyclin D1,estrogen receptor-alpha and survivin[J].Breast Cancer Res,2010,12(3):R32.
    [23]
    Hu Z,Gu Y,Han B,et al.Knockdown of AGR2 induces cellular senescence in prostate cancer cells[J].Carcinogenesis,2012,33(6):1178-1186.
    [24]
    Ma SR,Mao L,Deng WW,et al.AGR2 promotes the proliferation,migration and regulates epithelial-mesenchymal transition in salivary adenoid cystic carcinoma[J].Am J Transl Res,2017,9(2):507-519.
    [25]
    Wang Z,Hao Y,Lowe AW.The adenocarcinoma-associated antigen,AGR2,promotes tumor growth,cell migration,and cellular transformation[J].Cancer Res,2008,68(2):492-497.
    [26]
    Hollstein M,Sidransky D,Vogelstein B,et al.p53 mutations in human cancers[J].Science,1991,253(5015):49-53.
    [27]
    Hrstka R,Bouchalova P,Michalova E,et al.AGR2 oncoprotein inhibits p38 MAPK and p53 activation through a DUSP10-mediated regulatory pathway[J].Mol Oncol,2016,10(5):652-662.

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