您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报 (医学版) ›› 2023, Vol. 61 ›› Issue (11): 20-26.doi: 10.6040/j.issn.1671-7554.0.2023.0900

• 学术前沿 • 上一篇    下一篇

膀胱癌类器官模型的建立与应用进展

郭安东1,丁森泰1,2,*()   

  1. 1. 山东第一医科大学附属省立医院泌尿外科, 山东 济南 250012
    2. 山东大学附属山东省立医院泌尿外科, 山东 济南 250012
  • 收稿日期:2023-10-13 出版日期:2023-11-10 发布日期:2023-12-12
  • 通讯作者: 丁森泰 E-mail:dingsentai@126.com
  • 作者简介:丁森泰，医学博士，副教授，硕士研究生导师，山东大学附属山东省立医院泌尿外科副主任医师，日本京都大学联合培养博士，美国西南医学中心高级访问学者，济南市高层次人才。
    兼职有中华医学会山东省泌尿外科学会青年副主任委员，中国医师协会男科医师分会全国委员，中国抗癌协会泌尿男生殖系肿瘤专业委员会青年委员，山东省老年学与老年医学学会泌尿外科专业委员会副主任委员，山东省医学伦理学学会泌尿肿瘤外科分会第一届理事会副会长，山东省抗癌协会泌尿男生殖系肿瘤分会委员，山东省医药生物技术学会细胞治疗技术与标准化专业委员会常务委员，山东中西医结合学会男科专业委员会委员，山东省老年医学研究会男科学专业委员会委员等。
    从事泌尿外科医疗诊治10余年，对泌尿系肿瘤、结石及前列腺增生等良性病有丰富诊疗经验，对肾癌、前列腺癌等泌尿系常见肿瘤发病机制进行了深入研究，研究成果在SCI期刊发表论著20余篇，中文核心期刊论著20余篇；主持国家自然科学基金、山东省重点研发计划、山东省医药卫生科技发展计划和山东省自然科学、济南市科技发展计划等课题多项
  • 基金资助:
    山东省自然科学基金创新发展联合基金(ZR2023LZL005)

Progress in the establishment and application of organoids of bladder cancer

Andong GUO1,Sentai DING1,2,*()   

  1. 1. Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250012, Shandong, China
    2. Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
  • Received:2023-10-13 Online:2023-11-10 Published:2023-12-12
  • Contact: Sentai DING E-mail:dingsentai@126.com

RichHTML

15

PDF (PC)

192

摘要：

膀胱癌是临床常见的泌尿系统肿瘤, 以顺铂为主的化疗是不可手术和转移性肌层浸润性膀胱癌的一线治疗方案，而由于化疗耐药的产生，很大一部分患者会化疗失败，导致肿瘤复发和进展。肿瘤类器官模型近年来已成为研究发病转移机制和用药敏感性的热点，其中膀胱癌类器官的成功建立是膀胱癌临床转化研究的重大突破，类器官与原发组织具有高度的遗传和表型一致性，这种特性可以帮助我们更好地理解膀胱癌的基因组学改变、检测药物治疗敏感性以及耐药性等问题。本文旨在针对膀胱癌类器官作为临床前模型的构建流程、特征优势以及应用方向进行综述分析。

关键词: 类器官, 膀胱癌, 药物筛选, 肿瘤发病机制, 精准医疗

Abstract:

Bladder cancer is a common disease of the urinary system. Cisplatin-based chemotherapy is the first-line treatment for inoperable and metastatic myometrial invasive bladder cancer. However, due to resistance, a large number of patients fail in chemotherapy, which leads to tumor recurrence and progression. In recent years, organoid models have become a hot spot in the research of pathogenesis, metastasis and drug sensitivity. The successful establishment of bladder cancer organoids is a breakthrough in the clinical treatment of bladder cancer, because organoids and primary tissues have a high degree of genetic and phenotypic consistency, which can help us better understand the genomic changes of bladder cancer, and detect drug sensitivity and resistance. This article aims to review and analyze the construction process, characteristics, advantages and applications of bladder cancer organoids as preclinical models.

Key words: Organoids, Bladder cancer, Drug screening, Tumor pathogenesis, Precision medicine

中图分类号: 

  • R737.14

图1

膀胱癌类器官的培养与应用"

1 王凯剑, 戴利和, 许传亮. 膀胱癌分子分型的研究进展[J]. 第二军医大学学报, 2018, 39 (1): 81- 85.
doi: 10.16781/j.0258-879x.2018.01.0081
WANG Kaijian , DAI Lihe , XU Chuanliang . Molecular typing of bladder cancer: an update[J]. Academic Journal of Second Military Medical University, 2018, 39 (1): 81- 85.
doi: 10.16781/j.0258-879x.2018.01.0081
2 Jubber I , Ong S , Bukavina L , et al. Epidemiology of bladder cancer in 2023: a systematic review of risk factors[J]. Eur Urol, 2023, 84 (2): 176- 190.
doi: 10.1016/j.eururo.2023.03.029
3 Witjes JA , Bruins HM , Cathomas R , et al. European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines[J]. Eur Urol, 2021, 79 (1): 82- 104.
doi: 10.1016/j.eururo.2020.03.055
4 Compérat E , Amin MB , Cathomas R , et al. Current best practice for bladder cancer: a narrative review of diagnostics and treatments[J]. Lancet, 2022, 400 (10364): 1712- 1721.
doi: 10.1016/S0140-6736(22)01188-6
5 刘润泽, 张勇. 患者源性膀胱癌类器官模型的应用及研究进展[J]. 中华肿瘤防治杂志, 2023, 30 (15): 948- 952.
doi: 10.16073/j.cnki.cjcpt.2023.15.09
LIU Runze , ZHANG Yong . Application and research progress of patient-derived organoid model in bladder cancer[J]. Chinese Journal of Cancer Prevention and Treatment, 2023, 30 (15): 948- 952.
doi: 10.16073/j.cnki.cjcpt.2023.15.09
6 Clevers H . Modeling development and disease with organoids[J]. Cell, 2016, 165 (7): 1586- 1597.
doi: 10.1016/j.cell.2016.05.082
7 Huang L , Holtzinger A , Jagan I , et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell and patient-derived tumor organoids[J]. Nat Med, 2015, 21 (11): 1364- 1371.
doi: 10.1038/nm.3973
8 Homan KA , Gupta N , Kroll KT , et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro[J]. Nat Methods, 2019, 16 (3): 255- 262.
doi: 10.1038/s41592-019-0325-y
9 Roelofs C , Hollande F , Redvers R , et al. Breast tumour organoids: promising models for the genomic and functional characterisation of breast cancer[J]. Biochem Soc Trans, 2019, 47 (1): 109- 117.
doi: 10.1042/BST20180375
10 Lhmussaar K , Kopper O , Korving J , et al. Assessing the origin of high-grade serous ovarian cancer using CRISPR-modification of mouse organoids[J]. Nat Commun, 2020, 11 (1): 2660.
doi: 10.1038/s41467-020-16432-0
11 Lancaster MA , Knoblich JA . Generation of cerebral organoids from human pluripotent stem cells[J]. Nat Protoc, 2014, 9 (10): 2329- 2340.
doi: 10.1038/nprot.2014.158
12 Barker N , Huch M , Kujala P , et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro[J]. Cell Stem Cell, 2010, 6 (1): 25- 36.
doi: 10.1016/j.stem.2009.11.013
13 孙晓宇, 张志宏, 张昌文. 膀胱癌类器官模型的研究进展[J]. 天津医科大学学报, 2023, 29 (5): 564- 567.
14 Zhao X , Jiang Y , Liu C , et al. Organoid technology and clinical applications in digestive system cancer[J]. Engineering, 2022, 9 (2): 123- 130.
15 Medle B , Sj dahl G , Eriksson P , et al. Patient-derived bladder cancer organoid models in tumor biology and drug testing: a systematic review[J]. Cancers (Basel), 2022, 14 (9): 2062.
doi: 10.3390/cancers14092062
16 Bentivegna A , Conconi D , Panzeri E , et al. Biological heterogeneity of putative bladder cancer stem-like cell populations from human bladder transitional cell carcinoma samples[J]. Cancer Sci, 2010, 101 (2): 416- 424.
doi: 10.1111/j.1349-7006.2009.01414.x
17 Kim E , Choi S , Kang B , et al. Creation of bladder assembloids mimicking tissue regeneration and cancer[J]. Nature, 2020, 588 (7839): 664- 669.
doi: 10.1038/s41586-020-3034-x
18 Yu L , Li Z , Mei H , et al. Patient-derived organoids of bladder cancer recapitulate antigen expression profiles and serve as a personal evaluation model for CAR-T cells in vitro[J]. Clin Transl Immunology, 2021, 10 (2): e1248.
doi: 10.1002/cti2.1248
19 Walz S , Pollehne P , Geng R , et al. A protocol for organoids from the urine of bladder cancer patients[J]. Cells, 2023, 12 (17): 2188.
doi: 10.3390/cells12172188
20 Hofner T , Macher-Goeppinger S , Klein C , et al. Development and characteristics of preclinical experimental models for the research of rare neuroendocrine bladder cancer[J]. J Urol, 2013, 190 (6): 2263- 2270.
doi: 10.1016/j.juro.2013.06.053
21 Lee SH , Hu W , Matulay JT , et al. Tumor evolution and drug response in patient-derived organoid models of bladder cancer[J]. Cell, 2018, 173 (2): 515- 528.
doi: 10.1016/j.cell.2018.03.017
22 Shen L , Zhang J , Zheng Z , et al. PHGDH inhibits ferroptosis and promotes malignant progression by upregulating SLC7A11 in bladder cancer[J]. Int J Biol Sci, 2022, 18 (14): 5459- 5474.
doi: 10.7150/ijbs.74546
23 Wang M , Chen X , Tan P , et al. Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer[J]. Cancer Cell, 2022, 40 (9): 1044- 1059.
doi: 10.1016/j.ccell.2022.08.010
24 Mullenders J , de Jongh E , Brousali A , et al. Mouse and human urothelial cancer organ-oids: a tool for bladder cancer research[J]. Proc Natl Acad Sci U S A, 2019, 116 (10): 4567- 4574.
doi: 10.1073/pnas.1803595116
25 Wang N , Chen RX , Deng MH , et al. M5C-dependent cross-regulation between nuclear reader ALYREF and writer NSUN2 promotes urothelial bladder cancer malignancy through facilitating RABL6/TK1 mRNAs splicing and stabilization[J]. Cell Death Dis, 2023, 14 (2): 139.
doi: 10.1038/s41419-023-05661-y
26 Geng R , Harland N , Montes-Mojarro IA , et al. CD24: a marker for an extended expansion potential of urothelial cancer cell organoids in vitro[J]. Int J Mol Sci, 2022, 23 (10): 5453.
doi: 10.3390/ijms23105453
27 Xiao K , Peng S , Lu J , et al. UBE2S interacting with TRIM21 mediates the K11-linked ubiquitination of LPP to promote the lymphatic metastasis of bladder cancer[J]. Cell Death Dis, 2023, 14 (7): 408.
doi: 10.1038/s41419-023-05938-2
28 Vlaar JM , Borgman A , Kalkhoven E , et al. Recurrent exon-deleting activating mutations in AHR act as drivers of urinary tract cancer[J]. Sci Rep, 2022, 12 (1): 10081.
doi: 10.1038/s41598-022-14256-0
29 Kong J , Lee H , Kim D , et al. Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients[J]. Nat Commun, 2020, 11 (1): 5485.
doi: 10.1038/s41467-020-19313-8
30 Burgués JP , Gómez L , Pontones JL , et al. A chemosensitivity test for superficial bladder cancer based on three-dimensional culture of tumour spheroids[J]. Eur Urol, 2007, 51 (4): 962- 970.
doi: 10.1016/j.eururo.2006.10.034
31 Neal JT , Li X , Zhu J , et al. Organoid modeling of the tumor immune microenvironment[J]. Cell, 2018, 175 (7): 1972- 1988.
doi: 10.1016/j.cell.2018.11.021
32 Elbadawy M , Sato Y , Mori T , et al. Anti-tumor effect of trametinib in bladder cancer organoid and the underlying mechanism[J]. Cancer Biol Ther, 2021, 22 (5-6): 357- 371.
doi: 10.1080/15384047.2021.1919004
33 Abugomaa A , Elbadawy M , Ishihara Y , et al. Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids[J]. Front Pharmacol, 2023, 14, 1159516.
doi: 10.3389/fphar.2023.1159516
34 Gelbrich N , Miebach L , Berner J , et al. Medical gas plasma augments bladder cancer cell toxicity in preclinical models and patient-derived tumor tissues[J]. J Adv Res, 2023, 47, 209- 223.
doi: 10.1016/j.jare.2022.07.012
35 Seiler R , Egger M , De Menna M , et al. Guidance of adjuvant instillation in intermediate-risk non-muscle invasive bladder cancer by drug screens in patient derived organoids: a single center, open-label, phase Ⅱ trial[J]. BMC Urol, 2023, 23 (1): 89.
doi: 10.1186/s12894-023-01262-1
36 Becker L , Fischer F , Fleck JL , et al. Data-driven identification of biomarkers for in situ monitoring of drug treatment in bladder cancer organoids[J]. Int J Mol Sci, 2022, 23 (13): 6956.
doi: 10.3390/ijms23136956
37 Gong Z , Huang L , Tang X , et al. Acoustic droplet printing tumor organoids for modeling bladder tumor immune microenvironment within a week[J]. Adv Healthc Mater, 2021, 10 (22): e2101312.
doi: 10.1002/adhm.202101312
38 Yoon WH , Lee HR , Kim S , et al. Use of inkjet-printed single cells to quantify intratumoral heterogeneity[J]. Biofabrication, 2020, 12 (3): 035030.
doi: 10.1088/1758-5090/ab9491
39 Gheibi P , Zeng S , Son KJ , et al. Microchamber cultures of bladder cancer: a platform for characterizing drug responsiveness and resistance in PDX and primary cancer cells[J]. Sci Rep, 2017, 7 (1): 12277.
doi: 10.1038/s41598-017-12543-9
40 Lee LM , Seftor EA , Bonde G , et al. The fate of human malignant melanoma cells transplanted into zebrafish embryos: assessment of migration and cell division in the absence of tumor formation[J]. Dev Dyn, 2005, 233 (4): 1560- 1570.
doi: 10.1002/dvdy.20471
41 Marques IJ , Weiss FU , Vlecken DH , et al. Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model[J]. BMC Cancer, 2009, 9, 128.
doi: 10.1186/1471-2407-9-128
42 Ali Z , Vildevall M , Rodriguez GV , et al. Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer[J]. J Exp Clin Cancer Res, 2022, 41 (1): 58.
doi: 10.1186/s13046-022-02280-x
43 Wu ZS , Wu S . The era of personalized treatments: updates on immunotherapy within urothelial of bladder cancer[J]. Curr Urol, 2022, 16 (3): 117- 120.
doi: 10.1097/CU9.0000000000000133
[1] 马燕燕,龚瑶琴. 人脑类器官在神经发育疾病研究中的应用[J]. 山东大学学报 (医学版), 2021, 59(9): 22-29.
[2] 王琳琳,孙玉萍. 从临床医生角度,看人工智能在癌症精准诊疗中的应用及思考[J]. 山东大学学报 (医学版), 2021, 59(9): 89-96.
[3] 王传新. 肿瘤液体活检[J]. 山东大学学报 (医学版), 2021, 59(9): 64-71.
[4] 米琦,史爽,李娟,李培龙,杜鲁涛,王传新. 膀胱癌circRNAs介导的ceRNA网络及预后评估模型的构建[J]. 山东大学学报 (医学版), 2021, 59(6): 94-102.
[5] 张照鹏,邢乃栋,张翔,阎磊,徐忠华. 160例腹腔镜根治性膀胱切除术后淋巴漏的影响因素分析[J]. 山东大学学报 (医学版), 2020, 58(1): 67-72.
[6] 王健,李健,王勇,朱耀丰. 黄芩素通过抑制PI3K/AKT/mTOR通路诱导膀胱癌细胞凋亡[J]. 山东大学学报 (医学版), 2019, 57(9): 74-82.
[7] 刘杰, 崔伟,车梓,崔志强,王策正,王彤,李明,刘玲,杨全成,孙彬,高佃军,聂清生. 经尿道膀胱肿瘤电切术治疗肌层浸润性膀胱癌的临床疗效[J]. 山东大学学报 (医学版), 2018, 56(7): 81-85.
[8] 蒿魁元,赵圣,张宇,崔迪,荆翌峰,夏术阶,韩邦旻. 雄激素阻断对膀胱癌UM-UC-3细胞自噬与凋亡的影响[J]. 山东大学学报 (医学版), 2018, 56(3): 41-47.
[9] 王红阳. 精准医疗时代的肿瘤生物标志物发展[J]. 山东大学学报 (医学版), 2018, 56(10): 1-2.
[10] 刘益民，杜鲁涛，王丽丽，蒋秀梅，李娟，曲爱林，王海燕，郑桂喜，张欣，杨咏梅，王传新. 膀胱癌患者血清microRNA检测中内参基因的筛选及验证[J]. 山东大学学报（医学版）, 2014, 52(5): 86-91.
[11] 武广平，厉波，曹勇 . 钬激光联合吡柔比星膀胱灌注治疗非肌层浸润性膀胱癌的临床分析[J]. 山东大学学报(医学版), 2010, 48(12): 97-99.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 龙婷婷,谢明,周璐,朱俊德. Noggin蛋白对小鼠脑缺血再灌注损伤后学习和记忆能力与齿状回结构的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 15 -23 .
[2] 李宁,李娟,谢艳,李培龙,王允山,杜鲁涛,王传新. 长链非编码RNA AL109955.1在80例结直肠癌组织中的表达及对细胞增殖与迁移侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 38 -46 .
[3] 张宝文,雷香丽,李瑾娜,罗湘俊,邹容. miR-21-5p靶向调控TIMP3抑制2型糖尿病肾病小鼠肾脏系膜细胞增殖及细胞外基质堆积[J]. 山东大学学报 (医学版), 2020, 1(7): 7 -14 .
[4] 付洁琦,张曼,张晓璐,李卉,陈红. Toll样受体4抑制过氧化物酶体增殖物激活受体γ加重血脂蓄积的分子机制[J]. 山东大学学报 (医学版), 2020, 1(7): 24 -31 .
[5] 史爽,李娟,米琦,王允山,杜鲁涛,王传新. 胃癌miRNAs预后风险评分模型的构建与应用[J]. 山东大学学报 (医学版), 2020, 1(7): 47 -52 .
[6] 肖娟,肖强,丛伟,李婷,丁守銮,张媛,邵纯纯,吴梅,刘佳宁,贾红英. 两种甲状腺超声数据报告系统诊断效能的比较[J]. 山东大学学报 (医学版), 2020, 1(7): 53 -59 .
[7] 李松林,刘培来,卢群山,马贺然. 胫骨高位截骨术联合自体脂肪间充质干细胞注射在膝关节软骨修复中的应用[J]. 山东大学学报 (医学版), 2020, 1(7): 82 -88 .
[8] 徐继禧,陈伟健. 髓内弥漫性中线胶质瘤伴H3 K27M突变1例[J]. 山东大学学报 (医学版), 2020, 1(7): 96 -101 .
[9] 江涛. 类脑智能在脑科学的前沿应用[J]. 山东大学学报 (医学版), 2020, 1(8): 10 -13 .
[10] 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1 -6 .
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发