小鼠肿瘤肺转移模型及其应用进展

朱杨壮壮; 邹纯朴; 陈晓; 朱诗国; 韦璐瑶; 王莉新; 仲海荣; 张飞; 胥孜杭

doi:10.13422/j.cnki.syfjx.20190627

您当前的位置：

首页 >

文章列表页 >

小鼠肿瘤肺转移模型及其应用进展

中医药复方及其有效成分抗肺癌作用研究专题 | 更新时间：2021-02-09

- 小鼠肿瘤肺转移模型及其应用进展
- Research Progress and Application of Mouse Tumor Lung Metastasis Models
- 中国实验方剂学杂志 2019年25卷第14期页码：25-31
- 作者机构：
  
  1.上海中医药大学　基础医学院，经方理论应用研究中心，上海　 201203；
  2.上海交通大学　医学院　附属新华医院，上海　 200092
- 作者简介：
  
  朱杨壮壮，在读硕士，从事中药有效成分抗肿瘤的研究，E-mail：zyzz005@hotmail.com
  胥孜杭，师资博士后，从事中药有效成分抗肿瘤的研究，E-mail：xuzihang19881021@126.com
- 基金信息：
  
  上海市科学技术委员会科研计划项目(18YF1423500);经方理论应用研究中心项目(A1-Z183020110)
- DOI：10.13422/j.cnki.syfjx.20190627
  中图分类号： R22; R242; R2-031; R285.5;R287
- 收稿日期：2018-06-24，
  
  网络出版日期：2018-12-08，
  
  纸质出版日期：2019-07-20
- 稿件说明：
移动端阅览
朱杨壮壮, 邹纯朴, 陈晓, 等. 小鼠肿瘤肺转移模型及其应用进展[J]. 中国实验方剂学杂志, 2019,25(14):25-31.

Yang-zhuang-zhuang ZHU, Chun-pu ZOU, Xiao CHEN, et al. Research Progress and Application of Mouse Tumor Lung Metastasis Models[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(14): 25-31.
朱杨壮壮, 邹纯朴, 陈晓, 等. 小鼠肿瘤肺转移模型及其应用进展[J]. 中国实验方剂学杂志, 2019,25(14):25-31. DOI： 10.13422/j.cnki.syfjx.20190627.

Yang-zhuang-zhuang ZHU, Chun-pu ZOU, Xiao CHEN, et al. Research Progress and Application of Mouse Tumor Lung Metastasis Models[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(14): 25-31. DOI： 10.13422/j.cnki.syfjx.20190627.

摘要

尽管肿瘤的早期诊断和治疗手段不断提高，转移依然是导致恶性肿瘤患者死亡的主要原因。肺由于独特的生理、病理特征，是恶性肿瘤最容易发生远端转移的器官。肿瘤肺转移具有难以预测性，并且可能导致无法逆转的损伤。目前尚未发现肿瘤转移的确切机制和针对其有效的靶向防治手段。中医药凭借独特的辨证论治理论体系，在肿瘤肺转移的防治方面已有显著进展，但其应用方法和具体作用机制等仍待深入的研究和探索。为此，需要更精准、更符合临床疾病发生发展规律的动物模型作为研究媒介，故建立模拟肿瘤患者肺转移的动物模型已成为肿瘤肺转移研究的关键。通过介绍尾静脉注射法、乳垫注射法、皮下注射法、骨髓注射法、组织块原位移植法和基因工程小鼠等常用的肺转移模型的构建方法、应用以及评价，以期能够为研究肺转移小鼠模型的选择提供参考，为肿瘤肺转移的早期诊断、预防治疗及其发病原因、内在分子机制探索等提供更好的研究平台。此外，小鼠肺转移模型的发展还需思维广度及深度的拓展，对现有的模型合理、灵活的叠加运用及多学科的交叉合作，以建立更符合临床实际的动物模型，获得更可靠的研究结果。

Abstract

Early diagnoses and treatment methods are being constantly improved

but cancer metastasis remains a main cause of mortality in malignant tumor patients. Lung is thought to be the organ most prone to distal metastasis among malignant tumors due to its unique physiological and pathological character. Tumor lung metastasis is unpredictable and may result in irreversible damages. Presently

no exact mechanism or specific targeting therapies are found. Depending on the unique theory system-treatment based on symptom differentiation

traditional Chinese medicine has made significant progress on controlling tumor lung metastasis

but its application methods and mechanism still need further study and exploration. More appropriate and idealized animal models are required as a studying medium. Therefore

the establishment of animal models to simulate lung metastasis of cancer patients has become the key to the study of tumor lung metastasis. In order to produce a better platform for investigating the pathogenesis

underlying mechanism

early diagnosis and therapeutics for tumor lung metastasis

and to provide reference for the selection and establishment of mouse lung metastasis model

this article would introduce the implementation

application and estimation of several common methods (tail vein injection

mammary fat pad orthotopic injection

tibia injection

tissue orthotopic implantation

transgenic mice and so on). Meanwhile

the development of mouse lung metastasis model still needs expanding of thoughts

rational and flexible utilization of existing models

and interdisciplinary cooperation to establish preferable animal models and make results more reliable.

关键词

Keywords

references

陈万青，郑荣寿，张思维，等． 2013年中国恶性肿瘤发病和死亡分析 [J]．中国肿瘤， 2017 ， 26 ( 1 )： 1 - 7 ．

CHEN W , ZHENG R , Baade P D , et al . Cancer statistics in China, 2015 [J]. CA Cancer J Clin , 2016 , 66 ( 2 ): 115 - 132 .

Scully O J , Bay B H , Yip G , et al . Breast cancer metastasis [J]. Cancer Genomics Proteomics , 2012 , 9 ( 5 ): 311 - 320 .

Yeung T , Leung C S , Yip K , et al . Cellular and molecular processes in ovarian cancer metastasis.A review in the theme: cell and molecular processes in cancer metastasis [J]. Am J Physiol Cell Physiol , 2015 , 309 ( 7 ): C444 - C456 .

Sonnenschein C , Soto A M . Cancer metastases: so close and so far [J]. J Natl Cancer Inst , 2015 , 107 ( 11 ): 236 .

Thomas N S , Leanne C H . On the origin of cancer metastasis [J]. Crit Rev Oncog , 2013 , 18 ( 1/2 ): 43 - 73 .

Althagafi K T , Alashgar O A , Almaghrabi H S , et al . Missed pulmonary metastasis [J]. Asian Cardiovasc Thorac Ann , 2013 , 22 ( 2 ): 183 - 186 .

李佳桓，杜钢军，刘伟杰，等．牵牛子酒提取物对Lewis肺癌的抗肿瘤和抗转移机制研究 [J]．中国中药杂志， 2014 ， 39 ( 5 )： 879 - 884 ．

吕红，邹乐兰，麻俊超，等．三白草提取物抗乳腺癌转移作用及其机制研究 [J]．中国实验方剂学杂志， 2015 ， 21 ( 7 )： 123 - 127 ．

郭炜，董文亮，李坤星．桑黄云芝胶囊对Lewis肺癌自发肺转移模型小鼠的抑瘤作用 [J]．中国实验方剂学杂志， 2010 ， 16 ( 4 )： 128 - 130 ．

张永江，陈洪岩，夏长友．实验研究中实验动物的选择及其相关干扰因素 [J]．中国实验动物学杂志， 2002 ， 12 ( 5 )： 63 - 66 ．

WU G , Kim D , Kwon Park B , et al . Anti-metastatic effect of the TM4SF5-specific peptide vaccine and humanized monoclonal antibody on colon cancer in a mouse lung metastasis model [J]. Oncotarget , 2016 , 7 ( 48 ): 79170 - 78186 .

Linda C , Whitney B , Halina M O , et al . NF-kappaB activation within macrophages leads to an anti-tumor phenotype in a mammary tumor lung metastasis model [J]. Breast Cancer Res , 2011 , 13 ( 4 ): R83 .

WANG L , LIANG W , PENG N , et al . The synergistic antitumor effect of arsenic trioxide combined with cytotoxic T cells in pulmonary metastasis model of colon cancer [J]. Oncotarget , 2017 , 8 ( 65 ): 109609 - 109618 .

YANG R , Mondal G , Ness R A , et al . Polymer conjugate of a microtubule destabilizer inhibits lung metastatic melanoma [J]. J Control Release , 2017 , 249 : 32 - 41 .

Wieckowski S , Hemmerle T , Prince S S , et al . Therapeutic efficacy of the F8-IL2 immunocytokine in a metastatic mouse model of lung adenocarcinoma [J]. Lung Cancer , 2015 , 88 ( 1 ): 9 - 15 .

WANG L , HU X , XU Y , et al . Arsenic trioxide inhibits lung metastasis of mouse colon cancer via reducing the infiltration of regulatory T cells [J]. Tumor Biol , 2016 , 37 ( 11 ): 15165 - 15173 .

Tsai C H , CHENG H C , WANG Y S , et al . Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis [J]. Nat Commun , 2014 , doi: 10.1038/ncomms5804 http://doi.org/10.1038/ncomms5804 .

Lee E , Pandey N B , Popel A S . Pre-treatment of mice with tumor-conditioned media accelerates metastasis to lymph nodes and lungs: a new spontaneous breast cancer metastasis model [J]. Clin Exp Mstastas , 2014 , 31 ( 1 ): 67 - 79 .

刘晓，范萍，王水，等．小鼠人乳腺癌自发性肺转移模型的建立 [J]．中华实验外科杂志， 2003 ， 20 ( 7 )： 86 - 87 ．

Kocatürk B , Versteeg H H . Orthotopic injection of breast cancer cells into the mammary fat pad of mice to study tumor growth [J]. J Vis Exp , 2015 , ( 96 ): e51967 .

Lee H , YU H , Papadopoulos J N , et al . Targeted antivascular therapy with the apolipoprotein(a) kringle V, rhLK8, inhibits the growth and metastasis of human prostate cancer in an orthotopic nude mouse model [J]. Neo Plasia , 2012 , 14 ( 4 ): 335 - 343 .

Sasaki H , Iyer S V , Sasaki K , et al . An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma [J]. Anal Biochem , 2015 , 486 : 70 - 74 .

Katoh M , Neymaier M , Nezam R , et al . Correlation of circulating tumor cells with tumor size and metastatic load in a spontaneous lung metastasis model [J]. Anticancer Res , 2004 , 24 ( 3a ): 1421 - 1425 .

ZOU M , JIAO J , ZOU Q , et al . Multiple metastases in a novel LNCaP model of human prostate cancer [J]. Oncol Rep , 2013 , 30 ( 2 ): 615 - 622 .

Lobos-Gonzalez L , Aguilar-Guzmán L , Fernandez J G , et al . Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models [J]. Melanoma Res , 2014 , 24 ( 2 ): 108 - 119 .

杨宁，范清宇，殷剑宁，等．完整瘤组织块原位移植法建立人成骨肉瘤转移模型 [J]．癌症， 2000 ， 19 ( 10 )： 843 - 846 ．

Giuliano M , Herrera S , Christiny P , et al . Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis [J]. Breast Cancer Res , 2015 , doi: 10.1186/s13058-014-0508-5 http://doi.org/10.1186/s13058-014-0508-5 .

ZHANG X , Claerhout S , Prat A , et al . A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models [J]. Cancer Res , 2013 , 73 ( 15 ): 4885 - 4897 .

Melanie R R , Michael J A , Nikolaos S , et al . Initiation of metastatic breast carcinoma by targeting of the ductal epithelium with adenovirus-cre: a novel transgenic mouse model of breast cancer [J]. J Vis Exp , 2014 , 85 : e51171 .

More S K , Srinivasan N , Budnar S , et al . N-glycans and metastasis in galectin-3 transgenic mice [J]. Biochem Bioph Res Co , 2015 , 460 ( 2 ): 302 - 307 .

Rashid O M , Nagahashi M , Ramachandran S , et al . Is tail vein injection a relevant breast cancer lung metastasis model? [J] J Thorac Dis , 2013 , 5 ( 4 ): 385 - 392 .

Cutrera J , Johnson B , Ellis L , et al . Intraosseous inoculation of tumor cells cbone marrow promotes distant metastatic tumor development: a novel tool for mechanistic and therapeutic studies [J]. Cancer Lett , 2013 , 329 ( 1 ): 68 - 73 .

DU L , XU W T , FAN Q R , et al . Tumorigenesis and spontaneous metastasis by luciferase-labeled human xenogra osteosarcoma cells in nude mice [J]. Chin Med J , 2012 , 125 ( 22 ): 4022 - 4030 .

胥孜杭，胡洁淼，陈晓，等．小鼠肺癌模型研究进展 [J]．中国医药导报， 2016 ， 13 ( 9 )： 63 - 67 ．

FU X , Guadagni F , Hoffman R M . A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens [J]. Proc Natl Acad Sci USA , 1992 , 89 ( 12 ): 5645 - 5649 .

du Manoir S , Orsetti B , Bras-Gonçalves R , et al . Breast tumor PDXs are genetically plastic and correspond to a subset of aggressive cancers prone to relapse [J]. Mol Oncol , 2014 , 8 ( 2 ): 431 - 443 .

Zachary C D , Ashwini A K , Adam D S , et al . Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer [J]. Oncotarget , 2014 , 5 ( 18 ): 8750 - 8764 .

Paschall A V , LIU K . An orthotopic mouse model of spontaneous breast cancer metastasis [J]. J Vis Exp , 2016 , doi: 10.3791/54040 http://doi.org/10.3791/54040 .

ZHANG L , YE Y , YANG D , et al . Survivin and vascular endothelial growth factor are associated with spontaneous pulmonary metastasis of osteosarcoma: Development of an orthotopic mouse model [J]. Oncol Lett , 2014 , 8 ( 6 ): 2577 - 2580 .

Cassidy J W , Caldas C , Bruna A . Maintaining tumor heterogeneity in patient-derived tumor xenografts [J]. Cancer Res , 2015 , 75 ( 15 ): 2963 - 2968 .

REN C , Kumar S , Chanda D , et al . Therapeutic potential of mesenchymal stem cells producing interferon-α in a mouse melanoma lung metastasis model [J]. Stem Cells , 2008 , 26 ( 9 ): 2332 - 2338 .

Sitti R A H , Srikumar C , Kalanithi N , et al . Tocotrienol-adjuvanted dendritic cells inhibit tumor growth and metastasis: a murine model of breast cancer [J]. PLoS One , 2013 , 8 ( 9 ): e74753 .

Choi M , Kim S H , Chung W , et al . A natural sesquiterpenoid from Curcuma xanthorrhiza, has an anti-metastatic potential in experimental mouse lung metastasis model [J]. Biochem Bioph Res Co , 2004 , 326 ( 1 ): 210 - 217 .

PEI S , YANG X , WANG H , et al . Plantamajoside, a potential anti-tumor herbal medicine inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of matrix metalloproteinase-9 and-2 [J]. BMC Cancer , 2015 , doi: 10.1186/s12885-015-1960-z http://doi.org/10.1186/s12885-015-1960-z .

HUANG C C , LO C P , CHIU C Y , et al . Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice [J]. Br J Pharmacol , 2010 , 159 ( 4 ): 856 - 871 .

陈斌，罗跃华，王珊，等．裸花紫珠提取物的抗乳腺癌转移作用及其机制 [J]．中国实验方剂学杂志， 2015 ， 21 ( 18 )： 94 - 98 ．

廖明娟，王永灵，李琰，等．乳癌术后方及其拆方对乳腺癌肺转移模型小鼠Foxp3、TGF-β1、CD4＋的影响 [J]．上海中医药杂志， 2015 ， 49 ( 7 )： 77 - 81 ．

叶友友．芪癀胶囊对裸鼠原位移植骨肉瘤肺转移的作用及机制探讨 [D]．福州：福建中医药大学， 2014 ．

ZHU X , ZHOU Y , XU Q , et al . Traditional Chinese medicine Jianpi Bushen therapy suppresses the onset of pre-metastatic niche in a murine model of spontaneous lung metastasis [J]. Biomed Pharmacother , 2017 , 86 : 434 - 440 .

JIANG J H , Daisy W , Mengmeng Y , et al . Comprehensive characterization of chemotherapeutic efficacy on metastases in the established gastric neuroendocrine cancer patient derived xenograft model [J]. Oncotarget , 2015 , 6 ( 17 ): 15639 - 15651 .

Zaynagetdinov R , Sherrill T P , Gleaves L A , et al . Interleukin-5 facilitates lung metastasis by modulating the immune microenvironment [J]. Cancer Res , 2015 , 75 ( 8 ): 1624 - 1634 .

Terlizzi M , Popolo A , Pinto A , et al . Plasmacytoid dendritic cells contribute to doxorubicin-induced tumor arrest in a mouse model of pulmonary metastasis [J]. J Immunother , 2014 , 37 ( 4 ): 214 - 224 .

Fischer K R , Durrans A , Lee S , et al . Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance [J]. Nature , 2015 , 527 ( 7579 ): 472 - 476 .

Husmann K , Arlt M J E , Muff R , et al . Matrix Metalloproteinase 1 promotes tumor formation and lung metastasis in an intratibial injection osteosarcoma mouse model [J]. Biochim Biophys Acta , 2013 , 1832 ( 2 ): 347 - 354 .

Croker A K , Goodale D , Chu J , et al . High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability [J]. J Cell Mol Med . 2009 , 13 ( 8b ): 2236 - 2252 .

DeRose Y S , WANG G , LIN Y , et al . Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes [J]. Nat Med , 2011 , 17 ( 11 ): 1514 - 1520 .

Antonija K , John E D . Evolution of the cancer stem cell mModel [J]. Cell Stem Cell , 2014 , 14 ( 3 ): 275 - 291 .

肖毅，高江平，高昆，等．稳定表达hTERT/Luc的小鼠黑色毒瘤肺转移模型的建立 [J]．细胞与分子免疫学杂志， 2013 ， 29 ( 1 )： 89 - 92 ．

张文豪，李建军，杨德刚，等．双光子显微镜在小动物活体光学成像中的研究进展 [J]．中国康复理论与实践， 2017 ， 23 ( 1 )： 37 - 41 ．

ZHAO H , Nolley R , Chan A M W , et al . Cabozantinib inhibits tumor growth and metastasis of a patient-derived xenograft model of papillary renal cell carcinoma with MET mutation [J]. Cancer Biol Ther , 2017 , 18 ( 11 ): 863 - 871 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

天然阿拉伯半乳聚糖的来源，结构，生物活性及应用研究进展

中药精油治疗痛经的研究进展

青藏高原药用植物甘松研究进展

经典名方泻白散的源流及古今应用考究

《新型冠状病毒肺炎诊疗方案》推荐的中药注射剂治疗呼吸系统感染性疾病的研究进展