The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer.

The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer.
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DOI:
10.1002/jso.23316
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发表时间:
2013-06
影响因子:
2.5
通讯作者:
Mukherjee, Pinku
Mukherjee, Pinku
中科院分区:
医学3区
文献类型:
--
作者:
Curry, Jennifer M.;Thompson, Kyle J.;Rao, Shanti G.;Besmer, Dahlia M.;Murphy, Andrea M.;Grdzelishvili, Valery Z.;Ahrens, William A.;McKillop, Iain H.;Sindram, David;Iannitti, David A.;Martinie, John B.;Mukherjee, Pinku

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MUC 1在>60%的人胰腺癌(PC)中过度表达和异常糖基化。迫切需要开发用于检测和/或靶向MUC 1的新方法,并且应该能够检测PC细胞(包括癌症干细胞)和血清中的MUC 1。测定抗MUC 1抗体TAB 004的灵敏度和特异性。使用TAB 004-FITC在体外PC细胞系以及来自体内肿瘤和人类样本的谱系细胞上评估CSC的MUC 1表达。通过TAB 004 EIA评估血清的脱落MUC 1。在体外和体内,TAB 004在>95%的CSC上检测到MUC 1。通过TAB 004检测,患者中约80%的CSC显示MUC 1表达。在具有HPAF-II(MUC 1高)但不具有BxPC 3肿瘤(MUC 1低)的小鼠中检测到脱落的MUC 1血清。TAB 004 EIA能够准确检测PC患者的分期进展。TAB 004抗体可作为PC中CSC的治疗靶向剂进行探索。TAB 004 EIA以阶段依赖性方式检测PC患者的循环MUC 1,因此可作为PC阶段诊断生物标志物进行探索。
MUC1 is over-expressed and aberrantly glycosylated in >60% of human pancreatic cancer (PC). Development of novel approaches for detection and/or targeting of MUC1 are critically needed and should be able to detect MUC1 on PC cells (including cancer stem cells) and in serum. The sensitivity and specificity of the anti-MUC1 antibody, TAB 004, was determined. CSCs were assessed for MUC1 expression using TAB 004-FITC on in vitro PC cell lines, and on lineage− cells from in vivo tumors and human samples. Serum was assessed for shed MUC1 via the TAB 004 EIA. In vitro and in vivo, TAB 004 detected MUC1 on >95% of CSCs. Approximately, 80% of CSCs in patients displayed MUC1 expression as detected by TAB 004. Shed MUC1 was detected serum in mice with HPAF-II (MUC1high) but not BxPC3 tumors (MUC1low). The TAB 004 EIA was able to accurately detect stage progression in PC patients. The TAB 004 antibody may be explored as a therapeutic targeting agent for CSCs in PC. The TAB 004 EIA detected circulating MUC1 in a stage-dependent manner in patients with PC and thus may be explored as a PC stage diagnostic biomarker.
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