人骨髓基质干细胞抗原2在肿瘤发生发展中作用的研究进展
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摘要
人骨髓基质干细胞抗原2 (BST-2)是一种干扰素诱导的跨膜蛋白,最早作为B细胞终末分化的标记物而被发现,之后被鉴定为重要的可对抗艾滋病病毒(HIV)等包膜病毒的天然抗病毒因子。临床病理学分析、统计学数据和体内外实验研究表明BST-2同时具有促进肿瘤发生发展的能力。BST-2蛋白在乳腺癌、肺癌和鼻咽癌等多种癌症组织中高表达,其表达水平与患者生存期有关联。BST-2可促进癌细胞的迁移和侵袭,影响肿瘤的发生发展。BST-2促肿瘤进程的分子机制包括调控细胞DNA甲基化形式、对转化生长因子(TGF-β)的负调控作用、对细胞因子的诱导作用、对核因子κB (NF-κB)信号通路的激活以及促抗凋亡基因的表达等途径。破坏BST-2的分子结构、阻断其表达以及BST-2中和抗体的使用等已经在癌症治疗上体现出巨大价值。现综述BST-2对乳腺癌、肺癌、胃肠癌和鼻咽癌等不同癌症发生发展的影响,同时归纳其表达、转录后修饰及参与信号通路对其调控肿瘤发生发展的不同分子机制,揭示其作为肿瘤治疗潜在靶标的可能性。
引文
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[33]IKUSHIMA H,MIYAZONO K.TGFbeta signalling:a complex web in cancer progression[J].Nat Rev Cancer,2010,10(6):415-424.
[34]MAHAUAD-FERNANDEZ W D,BORCHERDING N C,ZHANG W Z,et al.Bone marrow stromal antigen 2(BST-2)DNA is demethylated in breast tumors and breast cancer cells[J].PLoS One,2015,10(4):e0123931.
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[37]ROMAGNOLO D F,DANIELS K D,Grunwald J T,et al.Epigenetics of breast cancer:Modifying role of environmental and bioactive food compounds[J].Mol Nutr Food Res,2016,60(6):1310-1329.
[38]HERMAN J G,BAYLIN S B.Gene silencing in cancer in association with promoter hypermethylation[J].N Engl JMed,2003,349(21):2042-2054.
[39]EHRLICH M.DNA hypomethylation,cancer,the immunodeficiency,centromeric region instability,facial anomalies syndrome and chromosomal rearrangements[J].J Nutr,2002,132(8Suppl):2424S-2429S.
[40]MAHAUAD-FERNANDEZ W D,OKEOMA C M.B49,a BST-2-based peptide,inhibits adhesion and growth of breast cancer cells[J].Sci Rep,2018,8(1):4305.
[41]SAYEED A,MENG Z,LUCIANI G,et al.Negative regulation of UCP2by TGFβsignaling characterizes low and intermediate-grade primary breast cancer[J].Cell Death Dis,2010,1:e53.
[42]WANG D,KANUMA T,MIZUNUMA H,et al.Analysis of specific gene mutations in the transforming growth factor-beta signal transduction pathway in human ovarian cancer[J].Cancer Res,2000,60(16):4507-4512.
[43]WEI D Y,LE X D,ZHENG L Z,et al.Stat3activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis[J].Oncogene,2003,22(3):319-329.
[44]XIE T X,HUANG F J,ALDAPE K D,et al.Activation of stat3in human melanoma promotes brain metastasis[J].Cancer Res,2006,66(6):3188-3196.
[45]CAI D Q,CAO J,LI Z,et al.Up-regulation of bone marrow stromal protein 2(BST2)in breast cancer with bone metastasis[J].BMC Cancer,2009,9:102.
[46]GALO R P,LE TORTOREC A,PICKERING S,et al.Innate sensing of HIV-1assembly by Tetherin induces NFκB-dependent proinflammatory responses[J].Cell Host Microbe,2012,12(5):633-644.
[2]HRECKA K,HAO C L,GIERSZEWSKA M,et al.Vpx relieves inhibition of HIV-1infection of macrophages mediated by the SAMHD1protein[J].Nature,2011,474(7353):658-661.
[3]SONG Y E,CYBURT D,LUCAS T M,et al.βTrCP is required for HIV-1Vpu modulation of CD4,GaLV Env,and BST-2/Tetherin[J].Viruses,2018,10(10):E573.
[4]CHANDE A,CUCCURULLO E C,ROSA A,et al.S2from equine infectious anemia virus is an infectivity factor which counteracts the retroviral inhibitors SERINC5 and SERINC3[J].Proc Natl Acad Sci U S A,2016,113(46):13197-13202.
[5]OHTOMO T,SUGAMATA Y,OZAKI Y,et al.Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells[J].Biochem Biophys Res Commun,1999,258(3):583-591.
[6]ISHIKAWA J,KAISHO T,TOMIZAWA H,et al.Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene,BST2,that may be involved in preB-cell growth[J].Genomics,1995,26(3):527-534.
[7]ERIKSON E,ADAM T,SCHMIDT S,et al.In vivo expression profile of the antiviral restriction factor and tumortargeting antigen CD317/BST-2/HM1.24/tetherin in humans[J].Proc Natl Acad Sci U S A,2011,108(33):13688-13693.
[8]SINGH H,SAMANI D,GHATE M V,et al.Impact of cellular restriction gene(TRIM5α,BST-2)polymorphisms on the acquisition of HIV-1 and disease progression[J].J Gene Med,2018,20(2/3):e3004.
[9]WANG M Y,ZHANG Z Y,WANG X J.Strain-specific antagonism of the human H1N1influenza A virus against equine tetherin[J].Viruses,2018,10(5):E264.
[10]HAN Z,LV M,SHI Y,et al.Mutation of glycosylation sites in BST-2 leads to its accumulation at intracellular CD63-positive vesicles without affecting its antiviral activity against multivesicular body-targeted HIV-1and hepatitis B virus[J].Viruses,2016,8(3):62.
[11]FU Y X,ZHANG L,ZHANG F,et al.Exosome-mediated miR-146atransfer suppresses type I interferon response and facilitates EV71infection[J].PLoS Pathog,2017,13(9):e1006611.
[12]MAHAUAD-FERNANDEZ W D,DEMALI K A,OLIVIERA K,et al.Bone marrow stromal antigen 2expressed in cancer cells promotes mammary tumor growth and metastasis[J].Breast Cancer Res,2014,16(6):493.
[13]WANG W,NISHIOKA Y,OZAKI S,et al.HM1.24(CD317)is a novel target against lung cancer for immunotherapy using anti-HM1.24 antibody[J].Cancer Immunol Immunother,2009,58(6):967-976.
[14]FANG K H,KAO H K,CHI L M,et al.Overexpression of BST2is associated with nodal metastasis and poorer prognosis in oral cavity cancer[J].Laryngoscope,2014,124(9):E354-E360.
[15]BLASIUS A L,GIURISATO E,CELLA M,et al.Bone marrow stromal cell antigen 2is a specific marker of typeⅠIFN-producing cells in the naive mouse,but a promiscuous cell surface antigen following IFN stimulation[J].J Immunol,2006,177(5):3260-3265.
[16]HINZ A,MIGUET N,NATRAJAN G,et al.Structural basis of HIV-1tethering to membranes by the BST-2/tetherin ectodomain[J].Cell Host Microbe,2010,7(4):314-323.
[17]SCHUBERT H.L,ZHAI Q T,SANDRIN V,et al.Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations[J].Proc Natl Acad Sci U S A,2010,107(42):17951-17956.
[18]SWIECKI M,SCHEAFFER S M,ALLAIRE M,et al.Structural and biophysical analysis of BST-2/tetherin ectodomains reveals an evolutionary conserved design to inhibit virus release[J].J Biol Chem,2011,286(4):2987-2997.
[19]ROLLASON R,KOROLCHUK V,HAMILTON C,et al.Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif[J].J Cell Sci,2007,120(Pt 21):3850-3858.
[20]MATSUDA A,SUZUKI Y,HONDA G,et al.Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways[J].Oncogene,2003,22(21):3307-3318.
[21]DUFRASNE F.E,LUCCHETTI M,MARTIN A,et al.Modulation of the NF-κB signaling pathway by the HIV-2envelope glycoprotein and its incomplete BST-2antagonism[J].Virology,2018,513:11-16.
[22]MUKAI S,OUE N,OSHIMA T,et al.Overexpression of transmembrane protein BST2is associated with poor survival of patients with esophageal,gastric,or colorectal cancer[J].Ann Surg Oncol,2017,24(2):594-602.
[23]SAYEED A,LUCIANI-TORRES G,MENG Z,et al.Aberrant regulation of the BST2(Tetherin)promoter enhances cell proliferation and apoptosis evasion in high grade breast cancer cells[J].PLoS One,2013,8(6):e67191.
[24]MAHAUAD-FERNANDEZ W D,OKEOMA C M.Cysteinelinked dimerization of BST-2 confers anoikis resistance to breast cancer cells by negating proapoptotic activities to promote tumor cell survival and growth[J].Cell Death Dis,2017,8(3):e2687.
[25]NAUSHAD W,MAHAUAD-FERNANDEZ W D,OKEOMAC M.Structural determinant of BST-2-mediated regulation of breast cancer cell motility:A role for cytoplasmic tail tyrosine residues[J].Oncotarget,2017,8(66):110221-110233.
[26]THAM T.Human papillomavirus and world health organization typeⅢnasopharyngeal carcinoma:Multicenter study from an endemic area in Southern China[J].Cancer,2019,125(1):161.
[27]CHIANG S F,KAN C Y,HSIAO Y C,et al.Bone marrow stromal antigen 2 is a novel plasma biomarker and prognosticator for colorectal carcinoma:A secretome-based verification study[J].Dis Markers,2015,2015:874054.
[28]PEGTEL D M,SUBRAMANIAN A,MERITT D,et al.IFN-alpha-stimulated genes and Epstein-Barr virus gene expression distinguish WHO typeⅡandⅢnasopharyngeal carcinomas[J].Cancer Res,2007,67(2):474-481.
[29]MERCIECA S,BELDERBOS J S A,VAN BAARDWIJK A,et al.The impact of training and professional collaboration on the interobserver variation of lung cancer delineations:a multiinstitutional study[J].Acta Oncol,2019,58(2):200-208.
[30]YU H L,WANG Y H,WANG S S,et al.Paclitaxel-loaded core-shell magnetic nanoparticles and cold atmospheric plasma inhibit non-small cell lung cancer growth[J].ACS Appl Mater Interfaces,2018,10(50):43462-43471.
[31]BECKER M,SOMMER A,KRTZSCHMAR J R,et al.Distinct gene expression patterns in a Tamoxifen-sensitive human mammary carcinoma xenograft and its Tamoxifenresistant subline MaCa 3366/TAM[J].Mol Cancer Ther,2005,4(1):151-168.
[32]HOTTER D,SAUTER D,KIRCHHOFF F.Emerging role of the host restriction factor tetherin in viral immune sensing[J].J Mol Biol,2013,425(24):4956-4964.
[33]IKUSHIMA H,MIYAZONO K.TGFbeta signalling:a complex web in cancer progression[J].Nat Rev Cancer,2010,10(6):415-424.
[34]MAHAUAD-FERNANDEZ W D,BORCHERDING N C,ZHANG W Z,et al.Bone marrow stromal antigen 2(BST-2)DNA is demethylated in breast tumors and breast cancer cells[J].PLoS One,2015,10(4):e0123931.
[35]WANG J C,BIAN S,LIU M C,et al.Cloning,identification,and functional analysis of bone marrow stromal cell antigen-2from sika deer(Cervus nippon)[J].Gene,2018,661:133-138.
[36]WU Y S,LEE Z Y,CHUAH L H,et al.Epigenetics in metastatic breast cancer:its regulation and implications in diagnosis,prognosis and therapeutics[J].Curr Cancer Drug Targets,2019,19(2):82-100.
[37]ROMAGNOLO D F,DANIELS K D,Grunwald J T,et al.Epigenetics of breast cancer:Modifying role of environmental and bioactive food compounds[J].Mol Nutr Food Res,2016,60(6):1310-1329.
[38]HERMAN J G,BAYLIN S B.Gene silencing in cancer in association with promoter hypermethylation[J].N Engl JMed,2003,349(21):2042-2054.
[39]EHRLICH M.DNA hypomethylation,cancer,the immunodeficiency,centromeric region instability,facial anomalies syndrome and chromosomal rearrangements[J].J Nutr,2002,132(8Suppl):2424S-2429S.
[40]MAHAUAD-FERNANDEZ W D,OKEOMA C M.B49,a BST-2-based peptide,inhibits adhesion and growth of breast cancer cells[J].Sci Rep,2018,8(1):4305.
[41]SAYEED A,MENG Z,LUCIANI G,et al.Negative regulation of UCP2by TGFβsignaling characterizes low and intermediate-grade primary breast cancer[J].Cell Death Dis,2010,1:e53.
[42]WANG D,KANUMA T,MIZUNUMA H,et al.Analysis of specific gene mutations in the transforming growth factor-beta signal transduction pathway in human ovarian cancer[J].Cancer Res,2000,60(16):4507-4512.
[43]WEI D Y,LE X D,ZHENG L Z,et al.Stat3activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis[J].Oncogene,2003,22(3):319-329.
[44]XIE T X,HUANG F J,ALDAPE K D,et al.Activation of stat3in human melanoma promotes brain metastasis[J].Cancer Res,2006,66(6):3188-3196.
[45]CAI D Q,CAO J,LI Z,et al.Up-regulation of bone marrow stromal protein 2(BST2)in breast cancer with bone metastasis[J].BMC Cancer,2009,9:102.
[46]GALO R P,LE TORTOREC A,PICKERING S,et al.Innate sensing of HIV-1assembly by Tetherin induces NFκB-dependent proinflammatory responses[J].Cell Host Microbe,2012,12(5):633-644.