姚伶俐①, 张丹芳①②, 赵秀兰①, 董学易①, 刘芳①, 林贤①, 孙俊英①, 郑旭①. DKK1 促进非小细胞肺癌线性程序性坏死和血管生成拟态形成*[J]. 中国肿瘤临床, 2016, 43(18): 797-803. DOI: 10.3969/j.issn.1000-8179.2016.18.807
引用本文: 姚伶俐①, 张丹芳①②, 赵秀兰①, 董学易①, 刘芳①, 林贤①, 孙俊英①, 郑旭①. DKK1 促进非小细胞肺癌线性程序性坏死和血管生成拟态形成*[J]. 中国肿瘤临床, 2016, 43(18): 797-803. DOI: 10.3969/j.issn.1000-8179.2016.18.807
Lingli YAO1, Danfang ZHANG1, 2, Xiulan ZHAO1, 2, Xueyi DONG1, Fang LIU1, Xian LIN1. DKK1 promotes linearly patterned programmed cell necrosis and vasculogenic mimicry in non-small cell lung cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2016, 43(18): 797-803. DOI: 10.3969/j.issn.1000-8179.2016.18.807
Citation: Lingli YAO1, Danfang ZHANG1, 2, Xiulan ZHAO1, 2, Xueyi DONG1, Fang LIU1, Xian LIN1. DKK1 promotes linearly patterned programmed cell necrosis and vasculogenic mimicry in non-small cell lung cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2016, 43(18): 797-803. DOI: 10.3969/j.issn.1000-8179.2016.18.807

DKK1 促进非小细胞肺癌线性程序性坏死和血管生成拟态形成*

DKK1 promotes linearly patterned programmed cell necrosis and vasculogenic mimicry in non-small cell lung cancer

  • 摘要: 目的:探讨非小细胞肺癌(non-small cell lung cancer ,NSCLC )中DKK 1 影响线性程序性坏死(linearly patterned programmed cellnecrosis ,LPPCN )和血管生成拟态(vasculogenic mimicry ,VM)的机制。方法:收集人NSCLC 标本173 例,H&E染色检测LP?PCN ,CD31/PAS 双染检测VM,免疫组织化学检测DKK 1 及相关蛋白表达,分析其临床病理意义及相互关系,进而裸鼠H 460-DKK 1 移植瘤体内验证研究假设。结果:NSCLC 中14.45%(25/ 173)存在VM,49.71%(86/ 173)具有LPPCN ,LPPCN (+)组25.6%(22/86)形成VM,二者均与分化差、TNM 分期晚、易复发转移和预后差相关。VM(+)组和LPPCN (+)组DKK 1 均高表达,均与VE-cad?herin、MMP-2、β -catenin 核表达及Twist1 正相关。H 460-DKK 1 移植瘤模型证实DKK 1 促进VM和LPPCN 及相关蛋白表达上调。结论:DKK 1 引起的β -catenin、Twist1 表达上调可促进NSCLC 中LPPCN 和VM形成。

     

    Abstract: Objective:To investigate the effect of DKK 1 on linearly patterned programmed cell necrosis (LPPCN) and vasculogenic mim-icry (VM) and the related molecular mechanism in non- small cell lung cancer (NSCLC). Methods:A total of 173 human NSCLC speci-mens were collected to detect LPPCN by H & E staining, detect VM with CD31/PAS double staining, and investigate DKK1 and related protein expression by immunohistochemistry. The clinical pathological significance of LPPCN, VM, and DKK 1 and the correlation of them were analyzed. Human NSCLC H 460 -DKK1 cells were engrafed in nude mice to evaluate the influence of DKK1 up-regulation on VM and LPPCN in vivo. Results:Approximately,14. 45% (25/173 ) of NSCLC had VM and 49. 71% (86/173 ) had LPPCN. 25. 6% (22/86) of NSCLC cases in LPPCN - positive group formed VM. Both of VM and LPPCN were all correlated with poor differentiation, late TNM stage, easy recurrence and metastasis and poor prognosis in NSCLC. DKK 1 expression in the VM-positive group and the LPPCN-positive group was higher than that in the VM-negative group and the LPPCN-negative group, respectively. DKK 1, LPPCN, and VM were positive -ly correlated with VE-cadherin, MMP- 2, β -catenin nuclear expression and Twist 1. H460 -DKK1 transplantation tumor model confirmed that DKK 1 promotes the expression of VM and LPPCN and related proteins in NSCLC. Conclusion: The increase of theβ - catenin and Twist1 expression induced by DKK 1 may promote the formation of LPPCN and VM in NSCLC.

     

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