BST-2参与HCMV感染诱导的恶性胶质瘤细胞增殖和迁移
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摘要
为探讨BST-2蛋白是否参与人巨细胞病毒(HCMV)感染导致的恶性胶质瘤细胞增殖和迁移,以HCMV AD169株感染U251细胞,通过细胞划痕愈合实验检测HCMV感染对U251迁移的影响;通过Western-blot方法检测HCMV感染对BST-2蛋白表达的影响;通过CCK-8、细胞划痕愈合和transwell方法检测HCMV感染后下调BST-2对U251细胞增殖和迁移能力的影响。结果显示,HCMV感染可促进U251细胞迁移并高表达BST-2,沉默BST-2后可抑制由HCMV感染诱导的细胞增殖和迁移。结果证实HCMV感染可促进胶质瘤细胞U251增殖迁移,BST-2参与了HCMV感染导致的恶性胶质瘤细胞增殖和迁移。
In order to investigate the effect of human cytomegalovirus(HCMV) on proliferation and migration of glioma cells and whether protein BST-2 participates in this process,U251 cells were infected by HCMV and the effect of HCMV infection on U251 migration were examined adopting wound-healing and Transwell assay. The effect of HCMV infection on the expression of BST-2 protein was detected by Western blot. The influence on cell proliferation and migration after down-regulation of BST-2 in HCMV infected U251 cells were detected by CCK-8,cell wound-healing assay and Transwell methods. The results revealed that HCMV infection can promote the migration of U251 cells and high expression of BST-2. After silencing BST-2 can inhibit the proliferation and migration induced by HCMV infection. These results have confirmed that HCMV infection can promote the proliferation and migration of glioma cells U251,and BST-2 has participated in the proliferation and migration of malignant glioma cells caused by HCMV infection.
In order to investigate the effect of human cytomegalovirus(HCMV) on proliferation and migration of glioma cells and whether protein BST-2 participates in this process,U251 cells were infected by HCMV and the effect of HCMV infection on U251 migration were examined adopting wound-healing and Transwell assay. The effect of HCMV infection on the expression of BST-2 protein was detected by Western blot. The influence on cell proliferation and migration after down-regulation of BST-2 in HCMV infected U251 cells were detected by CCK-8,cell wound-healing assay and Transwell methods. The results revealed that HCMV infection can promote the migration of U251 cells and high expression of BST-2. After silencing BST-2 can inhibit the proliferation and migration induced by HCMV infection. These results have confirmed that HCMV infection can promote the proliferation and migration of glioma cells U251,and BST-2 has participated in the proliferation and migration of malignant glioma cells caused by HCMV infection.
引文
[1]Cobbs CS,Harkins L,Samanta M,et al.Human cytomegalovirus infection and expression in human malignant glioma[J].Cancer Res,2002,62(12):3347-3350.
[2]Mitchell DA,Xie W,Schmittling R,et al.Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma[J].Neuro Oncol,2008,10(1):10-18.
[3]Scheurer ME,Bondy ML,Aldape KD,et al.Detection of human cytomegalovirus in different histological types of gliomas[J].Acta Neuropathol,2008,116(1):79-86.
[4]Wang X,Hu M,Xing F,et al.Human cytomegalovirus infection promotes the stemness of U251 glioma cells[J].J Med Virol,2016,89:878-886.
[5]Kupzig S,Korolchuk V,Rollason R,et al.Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology[J].Traffic,2003,4(10):694-709.
[6]Van Damme N,Goff D,Katsura C,et al.The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein[J].Cell Host Microbe,2008,3(4):245-252.
[7]Sarojini S,Theofanis T,Reiss CS.Interferon-induced tetherin restricts vesicular stomatitis virus release in neurons[J].DNA Cell Biol,2011,30(12):965-974.
[8]Lv M,Zhang B,Shi Y,et al.Identification of BST-2/tetherininduced hepatitis B virus restriction and hepatocyte-specific BST-2 inactivation[J].Sci Rep,2015,5(714):11736.
[9]Viswanathan K,Smith MS,Malouli D,et al.BST2/Tetherin enhances entry of human cytomegalovirus[J].PLo S Pathog,2011,7(11):e1002332.
[10]Mukai S,Oue N,Oshima T,et al.Overexpression of Transmembrane Protein BST2 is Associated with Poor Survival of Patients with Esophageal,Gastric,or Colorectal Cancer[J].Ann Surg Oncol,2017,24(2):594-602.
[11]Mahauad-Fernandez WD,De Mali KA,Olivier AK,et al.Bone marrow stromal antigen 2 expressed in cancer cells promotes mammary tumor growth and metastasis[J].Breast Cancer Res,2014,16(6):493.
[12]Fang KH,Kao HK,Chi LM,et al.Overexpression of BST2 is associated with nodal metastasis and poorer prognosis in oral cavity cancer[J].Laryngoscope,2014,124(9):E354-360.
[13]Wang W,Nishioka Y,Ozaki S,et al.HM1.24(CD317)is a novel target against lung cancer for immunotherapy using antiHM1.24 antibody[J].Cancer Immunol Immunother,2009,58(6):967-976.
[14]Mahauad-Fernandez WD,Borcherding NC,Zhang W,et al.Bone marrow stromal antigen 2(BST-2)DNA is demethylated in breast tumors and breast cancer cells[J].PLo S One,2015,10(4):e0123931.
[15]Milutin Gasperov N,Farkas SA,Nilsson TK,et al.Epigenetic activation of immune genes in cervical cancer[J].Immunol Lett,2014,162(2Pt B):256-257.
[16]Yokoyama T,Enomoto T,Serada S,et al.Plasma membrane proteomics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer[J].Int J Cancer,2013,132(2):472-484.
[17]Mahauad-Fernandez WD.The role of BST-2/Tetherin in host protection and disease manifestation[J].Immun Inflamm Dis,2016,4(1):4-23.
[18]Matsuda A,Suzuki Y,Honda G,et al.Large-scale identification and characterization of human genes that activate NF-kappa B and MAPK signaling pathways[J].Oncogene,2003,22(21):3307-3318.
[2]Mitchell DA,Xie W,Schmittling R,et al.Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma[J].Neuro Oncol,2008,10(1):10-18.
[3]Scheurer ME,Bondy ML,Aldape KD,et al.Detection of human cytomegalovirus in different histological types of gliomas[J].Acta Neuropathol,2008,116(1):79-86.
[4]Wang X,Hu M,Xing F,et al.Human cytomegalovirus infection promotes the stemness of U251 glioma cells[J].J Med Virol,2016,89:878-886.
[5]Kupzig S,Korolchuk V,Rollason R,et al.Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology[J].Traffic,2003,4(10):694-709.
[6]Van Damme N,Goff D,Katsura C,et al.The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein[J].Cell Host Microbe,2008,3(4):245-252.
[7]Sarojini S,Theofanis T,Reiss CS.Interferon-induced tetherin restricts vesicular stomatitis virus release in neurons[J].DNA Cell Biol,2011,30(12):965-974.
[8]Lv M,Zhang B,Shi Y,et al.Identification of BST-2/tetherininduced hepatitis B virus restriction and hepatocyte-specific BST-2 inactivation[J].Sci Rep,2015,5(714):11736.
[9]Viswanathan K,Smith MS,Malouli D,et al.BST2/Tetherin enhances entry of human cytomegalovirus[J].PLo S Pathog,2011,7(11):e1002332.
[10]Mukai S,Oue N,Oshima T,et al.Overexpression of Transmembrane Protein BST2 is Associated with Poor Survival of Patients with Esophageal,Gastric,or Colorectal Cancer[J].Ann Surg Oncol,2017,24(2):594-602.
[11]Mahauad-Fernandez WD,De Mali KA,Olivier AK,et al.Bone marrow stromal antigen 2 expressed in cancer cells promotes mammary tumor growth and metastasis[J].Breast Cancer Res,2014,16(6):493.
[12]Fang KH,Kao HK,Chi LM,et al.Overexpression of BST2 is associated with nodal metastasis and poorer prognosis in oral cavity cancer[J].Laryngoscope,2014,124(9):E354-360.
[13]Wang W,Nishioka Y,Ozaki S,et al.HM1.24(CD317)is a novel target against lung cancer for immunotherapy using antiHM1.24 antibody[J].Cancer Immunol Immunother,2009,58(6):967-976.
[14]Mahauad-Fernandez WD,Borcherding NC,Zhang W,et al.Bone marrow stromal antigen 2(BST-2)DNA is demethylated in breast tumors and breast cancer cells[J].PLo S One,2015,10(4):e0123931.
[15]Milutin Gasperov N,Farkas SA,Nilsson TK,et al.Epigenetic activation of immune genes in cervical cancer[J].Immunol Lett,2014,162(2Pt B):256-257.
[16]Yokoyama T,Enomoto T,Serada S,et al.Plasma membrane proteomics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer[J].Int J Cancer,2013,132(2):472-484.
[17]Mahauad-Fernandez WD.The role of BST-2/Tetherin in host protection and disease manifestation[J].Immun Inflamm Dis,2016,4(1):4-23.
[18]Matsuda A,Suzuki Y,Honda G,et al.Large-scale identification and characterization of human genes that activate NF-kappa B and MAPK signaling pathways[J].Oncogene,2003,22(21):3307-3318.