目的:探讨NEDD9和EZH2在乳腺浸润性导管癌中的表达及其与临床病理参数的关系,并分析其相关性。方法:收集郑州人民医院病理科2013年1月至2017年5月存档乳腺浸润性导管癌蜡块120例及30例正常乳腺组织,采用免疫组织化学Envision检测标本中N...目的:探讨NEDD9和EZH2在乳腺浸润性导管癌中的表达及其与临床病理参数的关系,并分析其相关性。方法:收集郑州人民医院病理科2013年1月至2017年5月存档乳腺浸润性导管癌蜡块120例及30例正常乳腺组织,采用免疫组织化学Envision检测标本中NEDD9和EZH2蛋白的表达情况。结果:乳腺浸润性导管癌组织中NEDD9和EZH2的阳性率分别为65%和80%,均高于正常乳腺组织,差异有统计学意义(P<0.05);NEDD9蛋白的表达与淋巴结转移、组织学分级、HER-2、雌激素受体(estrogen receptor,ER)及Ki-67增殖指数之间有统计学意义(P<0.05),与乳腺浸润性导管癌患者的年龄、肿瘤直径、TNM分期、孕激素受体(progesterone receptor,PR)均无统计学意义(P>0.05);EZH2蛋白的表达与淋巴结转移、HER-2、ER及Ki-67增殖指数之间有统计学意义相关(P<0.05),与乳腺浸润性导管癌患者的年龄、组织学分级、肿瘤直径、TNM分期、PR均无统计学意义(P>0.05);EZH2与NEDD9蛋白表达呈正相关(r s =0.308,P<0.05)。结论:乳腺浸润性导管癌中EZH2和NEDD9可能存在协同作用,二者高表达共同促进了乳腺浸润性导管癌的浸润、转移。展开更多
Objective:Esophageal squamous cell carcinoma(ESCC)has high morbidity and mortality rates worldwide.Cancer stem cells(CSCs)may cause tumor initiation,metastasis,and recurrence and are also responsible for chemotherapy ...Objective:Esophageal squamous cell carcinoma(ESCC)has high morbidity and mortality rates worldwide.Cancer stem cells(CSCs)may cause tumor initiation,metastasis,and recurrence and are also responsible for chemotherapy and radiotherapy failures.Myeloid-derived suppressor cells(MDSCs),in contrast,are known to be involved in mediating immunosuppression.Here,we aimed to investigate the mechanisms of interaction of CSCs and MDSCs in the tumor microenvironment.Methods:ESCC tissues and cell lines were evaluated.Neural precursor cell expressed,developmentally downregulated 9(NEDD9)was knocked down and overexpressed by lentiviral transfection.Quantitative PCR,Western blot,immunohistochemistry,cell invasion,flow cytometry,cell sorting,multiplex chemokine profiling,and tumor growth analyses were performed.Results:Microarray analysis revealed 10 upregulated genes in esophageal CSCs.Only NEDD9 was upregulated in CSCs using the sphere-forming method.NEDD9 expression was correlated with tumor invasion(P=0.0218),differentiation(P=0.0153),and poor prognosis(P=0.0373).Additionally,NEDD9 was required to maintain the stem-like phenotype.Screening of chemokine expression in ESCC cells with NEDD9 overexpression and knockdown showed that NEDD9 regulated C-X-C motif chemokine ligand 8(CXCL8)expression via the ERK pathway.CXCL8 mediated the recruitment of MDSCs induced by NEDD9 in vitro and in vivo.MDSCs promoted the stemness of ESCC cells through NEDD9 via the Notch pathway.Conclusions:As a marker of ESCC,NEDD9 maintained the stemness of ESCC cells and regulated CXCL8 through the ERK pathway to recruit MDSCs into the tumor,suggesting NEDD9 as a therapeutic target and novel prognostic marker for ESCC.展开更多
文摘目的:探讨NEDD9和EZH2在乳腺浸润性导管癌中的表达及其与临床病理参数的关系,并分析其相关性。方法:收集郑州人民医院病理科2013年1月至2017年5月存档乳腺浸润性导管癌蜡块120例及30例正常乳腺组织,采用免疫组织化学Envision检测标本中NEDD9和EZH2蛋白的表达情况。结果:乳腺浸润性导管癌组织中NEDD9和EZH2的阳性率分别为65%和80%,均高于正常乳腺组织,差异有统计学意义(P<0.05);NEDD9蛋白的表达与淋巴结转移、组织学分级、HER-2、雌激素受体(estrogen receptor,ER)及Ki-67增殖指数之间有统计学意义(P<0.05),与乳腺浸润性导管癌患者的年龄、肿瘤直径、TNM分期、孕激素受体(progesterone receptor,PR)均无统计学意义(P>0.05);EZH2蛋白的表达与淋巴结转移、HER-2、ER及Ki-67增殖指数之间有统计学意义相关(P<0.05),与乳腺浸润性导管癌患者的年龄、组织学分级、肿瘤直径、TNM分期、PR均无统计学意义(P>0.05);EZH2与NEDD9蛋白表达呈正相关(r s =0.308,P<0.05)。结论:乳腺浸润性导管癌中EZH2和NEDD9可能存在协同作用,二者高表达共同促进了乳腺浸润性导管癌的浸润、转移。
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81602599,31400752,81771781,and U1804281)the National Key Research and Development Program of China(Grant No.2016YFC1303501)。
文摘Objective:Esophageal squamous cell carcinoma(ESCC)has high morbidity and mortality rates worldwide.Cancer stem cells(CSCs)may cause tumor initiation,metastasis,and recurrence and are also responsible for chemotherapy and radiotherapy failures.Myeloid-derived suppressor cells(MDSCs),in contrast,are known to be involved in mediating immunosuppression.Here,we aimed to investigate the mechanisms of interaction of CSCs and MDSCs in the tumor microenvironment.Methods:ESCC tissues and cell lines were evaluated.Neural precursor cell expressed,developmentally downregulated 9(NEDD9)was knocked down and overexpressed by lentiviral transfection.Quantitative PCR,Western blot,immunohistochemistry,cell invasion,flow cytometry,cell sorting,multiplex chemokine profiling,and tumor growth analyses were performed.Results:Microarray analysis revealed 10 upregulated genes in esophageal CSCs.Only NEDD9 was upregulated in CSCs using the sphere-forming method.NEDD9 expression was correlated with tumor invasion(P=0.0218),differentiation(P=0.0153),and poor prognosis(P=0.0373).Additionally,NEDD9 was required to maintain the stem-like phenotype.Screening of chemokine expression in ESCC cells with NEDD9 overexpression and knockdown showed that NEDD9 regulated C-X-C motif chemokine ligand 8(CXCL8)expression via the ERK pathway.CXCL8 mediated the recruitment of MDSCs induced by NEDD9 in vitro and in vivo.MDSCs promoted the stemness of ESCC cells through NEDD9 via the Notch pathway.Conclusions:As a marker of ESCC,NEDD9 maintained the stemness of ESCC cells and regulated CXCL8 through the ERK pathway to recruit MDSCs into the tumor,suggesting NEDD9 as a therapeutic target and novel prognostic marker for ESCC.
