Nectin-1 is a marker of thyroid cancer sensitivity to herpes oncolytic therapy
Nectin-1 is a marker of thyroid cancer sensitivity to herpes oncolytic therapy
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DOI：
10.1210/jc.2007-0040
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发表时间：
2007-05-01
影响因子：
5.8
通讯作者：
Wong, Richard J.
中科院分区：
文献类型：
--
作者：
Huang, Yu-Yao;Yu, Zhenkun;Wong, Richard J.
背景：甲状腺未分化癌患者的预后很差，中位生存时间只有6个月。目的：我们的目标是评估减毒的、有复制能力的、溶瘤的疱疹病毒（NV 1023）进入并溶解人甲状腺癌的能力，并确定单纯疱疹病毒受体表达是否是NV 1023疗效的决定因素。设计：将一组由12种人甲状腺癌细胞系（包括间变性癌、髓样癌、滤泡癌和乳头状癌）暴露于NV 1023，并评估其对病毒侵入和溶瘤作用的敏感性。单纯疱疹病毒糖蛋白D受体nectin-1和疱疹病毒进入介体的表达进行了评估，通过定量荧光激活细胞分选仪和NV 1023的入口和oncolysis.Results相关：有显着的变化，NV 1023进入甲状腺癌细胞的能力，作为衡量lacZ的表达。甲状腺癌nectin-1表达与NV 1023进入密切相关。Nectin-1转染和抗体受体阻断研究验证了Nectin-1对NV 1023进入的重要性。滤泡癌对NV 1023溶瘤作用最不敏感。在感染复数为1时，暴露于NV 1023后7天，所有受试的间变性、髓样和乳头状癌均表现出大于85%的细胞毒性，尽管溶瘤作用在感染复数为0.01时是可变的。nectin-1的表达和NV 1023 oncolysis之间的显着相关性被确定使用Pearson的coefficients.Conclusions：NV 1023导致显着的细胞毒性的间变性，髓样和乳头状甲状腺癌。Nectin-1是甲状腺癌对疱疹溶瘤治疗敏感性的新标志物，可能指导患者选择治疗。
Context: The prognosis for patients diagnosed with anaplastic thyroid cancer is dismal, with a median survival time of only 6 months. Novel therapies are needed for these and other thyroid cancers that are refractory to conventional therapy.Objectives: Our goals were to assess the ability of an attenuated, replication-competent, oncolytic herpes virus (NV1023) to enter and lyse human thyroid cancers and determine whether herpes simplex virus receptor expression is a determinant of NV1023 efficacy.Design: A panel of 12 human thyroid cancer cell lines including anaplastic, medullary, follicular, and papillary cancers were exposed to NV1023 and assessed for susceptibility to viral entry and oncolysis. The expression of herpes simplex virus glycoprotein D receptors nectin-1 and herpes virus entry mediator was assessed by quantitative fluorescence-activated cell sorter and correlated with NV1023 entry and oncolysis.Results: There was significant variation in the ability of NV1023 to enter thyroid cancer cells as measured by lacZ expression. Thyroid cancer nectin-1 expression correlated strongly with NV1023 entry. Nectin-1 transfections and antibody receptor blocking studies validated the importance of nectin-1 for NV1023 entry. Follicular cancers were least sensitive to NV1023 oncolysis. All anaplastic, medullary, and papillary cancers tested exhibited greater than 85% cytotoxicity 7 d after exposure to NV1023 at multiplicity of infection 1, although oncolysis was variable at multiplicity of infection 0.01. Significant correlations between nectin-1 expression and NV1023 oncolysis were identified using Pearson's coefficients.Conclusions: NV1023 causes significant cytotoxicity of anaplastic, medullary, and papillary thyroid cancers. Nectin-1 is a novel marker of thyroid cancer sensitivity to herpes oncolytic therapy that might guide patient selection for therapy.