[1]陈 丹,王文静,王庆雅,等.生物发光成像技术在肿瘤细胞活体可视化研究中的应用研究进展[J].陕西医学杂志,2022,51(1):111-116.[doi:DOI:10.3969/j.issn.1000-7377.2022.01.028]
 CHEN Dan,WANG Wenjing,WANG Qingya,et al.Application of bioluminescence imaging technology in visualization of cancer cells in vivo[J].,2022,51(1):111-116.[doi:DOI:10.3969/j.issn.1000-7377.2022.01.028]
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生物发光成像技术在肿瘤细胞活体可视化研究中的应用研究进展
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年1期
页码:
111-116
栏目:
综 述
出版日期:
2022-01-05

文章信息/Info

Title:
Application of bioluminescence imaging technology in visualization of cancer cells in vivo
作者:
陈 丹王文静王庆雅曾 鋆詹勇华
(西安电子科技大学生命科学技术学院分子与神经影像教育部工程研究中心,陕西 西安 710126)
Author(s):
CHEN DanWANG WenjingWANG QingyaZENG YunZHAN Yonghua
(Engineering Research Centerof Molecular and Neuroimaging,Ministry of Education,School of Life Science and Technology,Xidian University,Xi'an 710126,China)
关键词:
生物发光成像 动物模型 荧光素酶 报告基因 可视化 肿瘤
Keywords:
Bioluminescence imaging Animal model Luciferase Reporter gene Visualization Cancer
分类号:
R 73-3
DOI:
DOI:10.3969/j.issn.1000-7377.2022.01.028
文献标志码:
A
摘要:
在肿瘤研究中,以小鼠和斑马鱼为主的动物模型实验作为介于体外细胞实验和临床试验之间重要的中间环节,往往很受青睐。近年来,挑选一些在肿瘤细胞进程中有特殊活性的启动子,构建这类启动子调控的荧光素酶报告基因,或者将荧光素酶基因的cDNA插入到肿瘤特异性表达的基因调控序列中,建立转基因小鼠和斑马鱼动物模型,随后通过生物发光成像技术(BLI),可以在活体动物模型中实现肿瘤细胞进程的可视化研究,包括对肿瘤细胞增殖、凋亡、迁移和免疫反应的实时监控。现综述利用BLI技术和活体动物成像模型在实现肿瘤细胞进程的可视化和确定肿瘤早期发展阶段方面的研究进展,及其用于不同组织器官间活动和肿瘤治疗方面的发展和应用。
Abstract:
As an important intermediate link between in vitro cell experiments and clinical experiments,animal models such as mice and zebrafish models are often preferred in cancer research.In recent years,some promoters with special activity in tumor progression have been selected to construct luciferase reporter genes.Moreover,to establish the transgenic mouse and zebrafish animal models,the cDNA of luciferase gene has been inserted into the regulation sequence of genes which have extra expression in cancer.Subsequently,through Bioluminescence Imaging(BLI),it makes it possible to visualization of tumor progression in vivo in living animal models,including real-time monitoring of cancer cell proliferation,apoptosis,migration and immune response.In this review,we summarize the advances in the use of BLI technology and in vivo animal imaging models to visualize cancer cell and identify early stages of tumor progression,as well as the development and application of BLI technology in the movement of different tissues and organs and cancer therapy.

参考文献/References:

[1] Signore A,Mather SJ,Piaggio G,et al.Molecular imaging of inflammation/infection:Nuclear medicine and optical imaging agents and methods[J].Chem Rev,2010,110(5):3112-3145.
[2] Manni I,Latouliere L,Gurtner A,et al.Transgenic animal models to visualize cancer-related cellular processes by bioluminescence imaging[J].Front Pharmacol,2019,10:235.
[3] Ciana P,Raviscioni M,Mussi P,et al.In vivo imaging of transcriptionally active estrogen receptors[J].Nat Med,2003,9(1):82-86.
[4] Chen CH,Durand E,Wang J,et al.Zebraflash transgenic lines for in vivo bioluminescence imaging of stem cells and regeneration in adult zebrafish[J].Development,2013,140(24):4988-4997.
[5] Goeman F,Manni I,Artuso S,et al.Molecular imaging of nuclear factor-Y transcriptional activity maps proliferation sites in live animals[J].Mol Biol Cell,2012,23(8):1467-1474.
[6] Principi E,Girardello R,Bruno A,et al.Systemic distribution of single-walled carbon nanotubes in a novel model:Alteration of biochemical parameters,metabolic functions,liver accumulation,and inflammation in vivo[J].Int J Nanomedicine,2016,11:4299-4316.
[7] Yamakoshi K,Takahashi A,Hirota F,et al.Real-time in vivo imaging of p16Ink4a reveals cross talk with p53[J].J Cell Biol,2009,186(3):393-407.
[8] Baker DJ,Wijshake T,Tchkonia T,et al.Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders[J].Nature,2011,479(7372):232-236.
[9] Burd CE,Sorrentino JA,Clark KS,et al.Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model[J].Cell,2013,152(1-2):340-351.
[10] Sorrentino JA,Krishnamurthy J,Tilley S,et al.p16INK4a reporter mice reveal age-promoting effects of environmental toxicants[J].J Clin Invest,2014,124(1):169-173.
[11] Ohtani N,Imamura Y,Yamakoshi K,et al.Visualizing the dynamics of p21(Waf1/Cip1)cyclin-dependent kinase inhibitor expression in living animals[J].Proc Natl Acad Sci USA,2007,104(38):15034-15039.
[12] Tinkum KL,Marpegan L,White LS,et al.Bioluminescence imaging captures the expression and dynamics of endogenous p21 promoter activity in living mice and intact cells[J].Mol Cell Biol,2011,31(18):3759-3772.
[13] Mcmahon M,Frangova TG,Henderson CJ,et al.Olaparib,monotherapy or with ionizing radiation,exacerbates DNA damage innormal tissues:Insights from a new p21 reporter mouse[J].Mol Cancer Res,2016,14(12):1195-1203.
[14] Hamstra DA,Bhojani MS,Griffin LB,et al.Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging[J].Cancer Res,2006,66(15):7482-7489.
[15] Briat A,Vassaux G.A new transgenic mouse line to image chemically induced p53 activation in vivo[J].Cancer Sci,2008,99(4):683-688.
[16] 郭 黎,王 静.核因子-κB信号通路对肺炎模型小鼠免疫功能和炎症反应的影响[J].陕西医学杂志,2020,49(11):1383-1386.
[17] Hettinghouse A,Fu W,Liu CJ.Monitoring atsttrin-mediated inhibition of TNFalpha/NF-kappabeta activation through in vivo bioluminescence imaging[J].Methods Mol Biol,2021,2248:201-210.
[18] Ishikawa TO,Jain NK,Taketo MM,et al.Imaging cyclooxygenase-2(Cox-2)gene expression in living animals with a luciferase knock-in reporter gene[J].Mol Imaging Biol,2006,8(3):171-187.
[19] Hayashi M,Takai J,Yu L,et al.Whole-body in vivo monitoring of inflammatory diseases exploiting human interleukin 6-luciferase transgenic mice[J].Mol Cell Biol,2015,35(20):3590-3601.
[20] Rauch D,Gross S,Harding J,et al.Imaging spontaneous tumorigenesis:Inflammation precedes development of peripheral NK tumors[J].Blood,2009,113(7):1493-1500.
[21] Rauch D,Gross S,Harding J,et al.T-cell activation promotes tumorigenesis in inflammation-associated cancer[J].Retrovirology,2009,6:116.
[22] Szyska M,Herda S,Althoff S,et al.A transgenic dual-luciferase reporter mouse for longitudinal and functional monitoring of T cells in vivo[J].Cancer Immunol Res,2018,6(1):110-120.
[23] Suffner J,Hochweller K,Kühnle MC,et al.Dendritic cells support homeostatic expansion of Foxp3 + regulatory T cells in Foxp3.LuciDTR mice[J].J Immunol,2010,184(4):1810-1820.
[24] Chewning JH,Dugger KJ,Chaudhuri TR,et al.Bioluminescence-based visualization of CD4 T cell dynamics using a T lineage-specific luciferase transgenic model[J].BMC Immunol,2009,10:44.
[25] Vooijs M,Jonkers J,Lyons S,et al.Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice[J].Cancer Res,2002,62(6):1862-1867.
[26] Momota H,Holland EC.Bioluminescence technology for imaging cell proliferation[J].Curr Opin Biotechnol,2005,16(6):681-686.
[27] Lyons SK,Lim E,Clermont AO,et al.Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice[J].Cancer Res,2006,66(9):4701-4707.
[28] Seethammagari MR,Xie X,Greenberg NM,et al.EZC-prostate models offer high sensitivity and specificity for noninvasive imaging of prostate cancer progression and androgen receptor action[J].Cancer Res,2006,66(12):6199-6209.
[29] Koppens MA,Tanger E,Nacerddine K,et al.A new transgenic mouse model for conditional overexpression of the polycomb group protein EZH2[J].Transgenic Res,2017,26(2):187-196.
[30] Lu X,Guo H,Molter J,et al.Alpha-fetoprotein-thymidine kinase-luciferase knockin mice:A novel model for dual modality longitudinal imaging of tumorigenesis in liver[J].J Hepatol,2011,55(1):96-102.
[31] Park JH,Kim KI,Lee YJ,et al.Non-invasive monitoring of hepatocellular carcinoma in transgenic mouse with bioluminescent imaging[J].Cancer Lett,2011,310(1):53-60.
[32] Ju HL,Calvisi DF,Moon H,et al.Transgenic mouse model expressing P53(R172H),luciferase,EGFP,and KRAS(G12D)in a single open reading frame for live imaging of tumor[J].Sci Rep,2015,5:8053.
[33] Ju HL,Calvisi DF,Moon H,et al.Transgenic mouse model expressing P53(R172H),luciferase,EGFP,and KRAS(G12D)in a single open reading frame for live imaging of tumor[J].Sci Rep,2015,5:8053.
[34] Zumsteg A,Strittmatter K,Klewe-Nebenius D,et al.A bioluminescent mouse model of pancreatic β-cell carcinogenesis[J]. Carcinogenesis, 2010, 31(8):1465-1474.
[35] De-Latouliere L,Manni I,Iacobini C,et al.A bioluminescent mouse model of proliferation to highlight early stages of pancreatic cancer:A suitable tool for preclinical studies[J].Ann Anat,2016,207:2-8.
[36] Zhong R,Pytynia M,Pelizzari C,et al.Bioluminescent imaging of HPV-positive oral tumor growth and its response to image-guided radiotherapy[J].Cancer Res,2014,74(7):2073-2081.
[37] Zagozdzon AM,Leary P,Callanan JJ,et al.Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice[J].BMC Cancer,2012,12:209.
[38] Marchini C,Gabrielli F,Iezzi M,et al.The human splice variant Δ16HER2 induces rapid tumor onset in a reporter transgenic mouse[J].PLoS One,2011,6(4):e18727.
[39] Goldman SJ,Chen E,Taylor R,et al.Use of the ODD-luciferase transgene for the non-invasive imaging of spontaneous tumors in mice[J].PLoS One,2011,6(3):e18269.
[40] Jia W,Wang S,Horner JW,et al.A BAC transgenic reporter recapitulates in vivo regulation of human telomerase reverse transcriptase in development and tumorigenesis[J].Faseb J,2011,25(3):979-989.
[41] Vantaggiato C,Dellomo G,Ramachandran B,et al.Bioluminescence imaging of estrogen receptor activity during breast cancer progression[J].Am J Nucl Med Mol Imaging,2016,6(1):32-41.
[42] Astuti Y,Kramer AC,Blake AL,et al.A functional bioluminescent zebrafish screen for enhancing hematopoietic cell homing[J].Stem Cell Reports,2017,8(1):177-190.
[43] Letrado P,De-Miguel I,Lamberto I,et al.Zebrafish: Speeding up the cancer drug discovery process[J].Cancer Res,2018,78(21):6048-6058.
[44] Fan F,Wood KV.Bioluminescent assays for high-throughput screening[J].Assay Drug Dev Technol,2007,5(1):127-136.
[45] Czupryna J,Tsourkas A.Firefly luciferase and RLuc8 exhibit differential sensitivity to oxidative stress in apoptotic cells[J].PLoS One,2011,6(5):e20073.
[46] Berger F,Paulmurugan R,Bhaumik S,et al.Uptake kinetics and biodistribution of 14C-D-luciferin-a radiolabeled substrate for the firefly luciferase catalyzed bioluminescence reaction:Impact on bioluminescence based reporter gene imaging[J].Eur J Nucl Med Mol Imaging,2008,35(12):2275-2285.
[47] Edinger M,Cao YA,Hornig YS,et al.Advancing animal models of neoplasia through in vivo bioluminescence imaging[J].Eur J Cancer,2002,38(16):2128-2136.
[48] 梁 天,朱晓明.趋化因子CCL28研究进展及其与肿瘤的关系[J].陕西医学杂志,2019,48(6):813-814.
[49] Becker JC.Tumor-educated myeloid cells:impact the micro- and macroenvironment [J].Exp Dermatol,2014,23(3):157-158.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(91859109,32001074); 陕西省自然科学基础研究计划项目(2020JM-209); 人因工程重点实验室基础研究基金对外开放基金资助项目(SYFD061908K); 中央高校基本科研业务费资助项目(JB211206)
更新日期/Last Update: 2022-01-09