• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

具有驱动突变肿瘤内异质性的工程化胰腺癌模型。

An engineered pancreatic cancer model with intra-tumoral heterogeneity of driver mutations.

机构信息

School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA.

出版信息

Lab Chip. 2020 Oct 21;20(20):3720-3732. doi: 10.1039/d0lc00707b. Epub 2020 Sep 10.

DOI:10.1039/d0lc00707b
PMID:32909573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9178523/
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a complex disease with significant intra-tumoral heterogeneity (ITH). Currently, no reliable PDAC tumor model is available that can present ITH profiles in a controlled manner. We develop an in vitro microfluidic tumor model mimicking the heterogeneous accumulation of key driver mutations of human PDAC using cancer cells derived from genetically engineered mouse models. These murine pancreatic cancer cell lines have KPC (Kras and Trp53 mutations) and KIC genotypes (Kras mutation and Cdkn2a deletion). Also, the KIC genotypes have two distinct phenotypes - mesenchymal or epithelial. The tumor model mimics the ITH of human PDAC to study the effects of ITH on the gemcitabine response. The results show gemcitabine resistance induced by ITH. Remarkably, it shows that cancer cell-cell interactions induce the gemcitabine resistance potentially through epithelial-mesenchymal-transition. The tumor model can provide a useful testbed to study interaction mechanisms between heterogeneous cancer cell subpopulations.

摘要

胰腺导管腺癌 (PDAC) 是一种具有显著肿瘤内异质性 (ITH) 的复杂疾病。目前，尚无可靠的 PDAC 肿瘤模型能够以可控的方式呈现 ITH 特征。我们开发了一种体外微流控肿瘤模型，使用源自基因工程小鼠模型的癌细胞模拟人类 PDAC 关键驱动突变的异质性积累。这些小鼠胰腺癌细胞系具有 KPC（Kras 和 Trp53 突变）和 KIC 基因型（Kras 突变和 Cdkn2a 缺失）。此外，KIC 基因型具有两种不同的表型 - 间充质或上皮。肿瘤模型模拟人类 PDAC 的 ITH，以研究 ITH 对吉西他滨反应的影响。结果表明，ITH 诱导吉西他滨耐药。值得注意的是，它表明癌细胞-细胞相互作用可能通过上皮-间充质转化诱导吉西他滨耐药。该肿瘤模型可为研究异质癌细胞亚群之间的相互作用机制提供一个有用的试验台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/8434b22a1d6b/nihms-1810623-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/c02c39e61f78/nihms-1810623-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/5a29184648f9/nihms-1810623-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/7b95a317e975/nihms-1810623-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/b4d26c8ebb25/nihms-1810623-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/b02eeb63ac84/nihms-1810623-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/8434b22a1d6b/nihms-1810623-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/c02c39e61f78/nihms-1810623-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/5a29184648f9/nihms-1810623-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/7b95a317e975/nihms-1810623-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/b4d26c8ebb25/nihms-1810623-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/b02eeb63ac84/nihms-1810623-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0491/9178523/8434b22a1d6b/nihms-1810623-f0006.jpg

相似文献

1
An engineered pancreatic cancer model with intra-tumoral heterogeneity of driver mutations.具有驱动突变肿瘤内异质性的工程化胰腺癌模型。
Lab Chip. 2020 Oct 21;20(20):3720-3732. doi: 10.1039/d0lc00707b. Epub 2020 Sep 10.
2
A Biomimetic Tumor Model of Heterogeneous Invasion in Pancreatic Ductal Adenocarcinoma.一种胰腺导管腺癌异质浸润的仿生肿瘤模型。
Small. 2020 Mar;16(10):e1905500. doi: 10.1002/smll.201905500. Epub 2020 Jan 30.
3
Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer via Gata6-dependent dedifferentiation of acinar cells in mice.尼古丁通过 Gata6 依赖性去分化胰腺腺泡细胞促进 KRAS 诱导的胰腺癌的发生和进展。
Gastroenterology. 2014 Nov;147(5):1119-33.e4. doi: 10.1053/j.gastro.2014.08.002. Epub 2014 Aug 12.
4
Genetic inactivation of Nupr1 acts as a dominant suppressor event in a two-hit model of pancreatic carcinogenesis.Nupr1 的遗传失活在胰腺发生的两次打击致癌模型中充当显性抑制事件。
Gut. 2014 Jun;63(6):984-95. doi: 10.1136/gutjnl-2013-305221. Epub 2013 Sep 11.
5
Novel pancreatic cancer cell lines derived from genetically engineered mouse models of spontaneous pancreatic adenocarcinoma: applications in diagnosis and therapy.新型胰腺癌细胞系源自自发性胰腺腺癌的基因工程小鼠模型：在诊断和治疗中的应用。
PLoS One. 2013 Nov 20;8(11):e80580. doi: 10.1371/journal.pone.0080580. eCollection 2013.
6
Intratumor Heterogeneity of KRAS Mutation Status in Pancreatic Ductal Adenocarcinoma Is Associated With Smaller Lesions.胰腺导管腺癌中KRAS突变状态的肿瘤内异质性与较小病变相关。
Pancreas. 2016 Jul;45(6):876-81. doi: 10.1097/MPA.0000000000000562.
7
Inactivation of APC Induces CD34 Upregulation to Promote Epithelial-Mesenchymal Transition and Cancer Stem Cell Traits in Pancreatic Cancer.APC 的失活诱导 CD34 上调，促进胰腺癌中的上皮-间充质转化和癌症干细胞特征。
Int J Mol Sci. 2020 Jun 23;21(12):4473. doi: 10.3390/ijms21124473.
8
CXCR4 in Tumor Epithelial Cells Mediates Desmoplastic Reaction in Pancreatic Ductal Adenocarcinoma.肿瘤上皮细胞中的 CXCR4 介导胰腺导管腺癌的促结缔组织反应。
Cancer Res. 2020 Oct 1;80(19):4058-4070. doi: 10.1158/0008-5472.CAN-19-2745. Epub 2020 Jun 30.
9
Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma.代谢编程对不同的癌症干细胞的促进作用，推动了胰腺导管腺癌的转移。
Oncogene. 2021 Jan;40(1):215-231. doi: 10.1038/s41388-020-01518-2. Epub 2020 Oct 27.
10
Cell of origin affects tumour development and phenotype in pancreatic ductal adenocarcinoma.起源细胞影响胰腺导管腺癌的肿瘤发生和表型。
Gut. 2019 Mar;68(3):487-498. doi: 10.1136/gutjnl-2017-314426. Epub 2018 Jan 23.

引用本文的文献

1
Statin-dye conjugates for selective targeting of mutant cancer cells.用于选择性靶向突变癌细胞的他汀类药物-染料缀合物。
bioRxiv. 2025 Jun 6:2025.06.03.657329. doi: 10.1101/2025.06.03.657329.
2
DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells.用于KRAS突变型胰腺癌细胞精准成像的DNA折纸-花菁纳米复合物
Adv Sci (Weinh). 2025 May;12(19):e2410278. doi: 10.1002/advs.202410278. Epub 2025 Feb 14.
3
Targeted Cancer Therapy-on-A-Chip.靶向癌症治疗芯片

本文引用的文献

1
A Tumor-on-a-Chip System with Bioprinted Blood and Lymphatic Vessel Pair.一种具有生物打印的血管和淋巴管对的芯片肿瘤系统。
Adv Funct Mater. 2019 Aug 1;29(31). doi: 10.1002/adfm.201807173. Epub 2019 May 1.
2
Assessing Cell Activities rather than Identities to Interpret Intra-Tumor Phenotypic Diversity and Its Dynamics.评估细胞活性而非细胞身份以解释肿瘤内表型多样性及其动态变化。
iScience. 2020 May 22;23(5):101061. doi: 10.1016/j.isci.2020.101061. Epub 2020 Apr 13.
3
A Biomimetic Tumor Model of Heterogeneous Invasion in Pancreatic Ductal Adenocarcinoma.
Adv Healthc Mater. 2024 Nov;13(29):e2400833. doi: 10.1002/adhm.202400833. Epub 2024 Aug 5.
4
New Ref-1/APE1 targeted inhibitors demonstrating improved potency for clinical applications in multiple cancer types.新型 Ref-1/APE1 靶向抑制剂在多种癌症类型的临床应用中显示出更高的效力。
Pharmacol Res. 2024 Mar;201:107092. doi: 10.1016/j.phrs.2024.107092. Epub 2024 Feb 2.
5
Microphysiological systems as reliable drug discovery and evaluation tools: Evolution from innovation to maturity.微生理系统作为可靠的药物发现和评估工具：从创新到成熟的演进
Biomicrofluidics. 2023 Dec 28;17(6):061504. doi: 10.1063/5.0179444. eCollection 2023 Dec.
6
Advanced manufacturing of nanoparticle formulations of drugs and biologics using microfluidics.利用微流控技术实现药物和生物制剂的纳米颗粒制剂的先进制造。
Analyst. 2024 Jan 29;149(3):614-637. doi: 10.1039/d3an01739g.
7
Inkjet-printed morphogenesis of tumor-stroma interface using bi-cellular bioinks of collagen-poly(N-isopropyl acrylamide-co-methyl methacrylate) mixture.使用胶原蛋白-聚（N-异丙基丙烯酰胺-共-甲基丙烯酸甲酯）混合物的双细胞生物墨水通过喷墨打印实现肿瘤-基质界面的形态发生
Mater Today Adv. 2023 Aug;19. doi: 10.1016/j.mtadv.2023.100408. Epub 2023 Aug 2.
8
Optically induced electrothermal microfluidic tweezers in bio-relevant media.光诱导电热微流控镊子在生物相关介质中的应用。
Sci Rep. 2023 Jun 17;13(1):9819. doi: 10.1038/s41598-023-35722-3.
9
A timescale-guided microfluidic synthesis of tannic acid-Fe network nanocapsules of hydrophobic drugs.基于时标引导的单宁酸-Fe 网络纳米胶囊的微流体制备用于疏水性药物。
J Control Release. 2023 May;357:484-497. doi: 10.1016/j.jconrel.2023.04.024. Epub 2023 Apr 21.
10
Cells function as a ternary logic gate to decide migration direction under integrated chemical and fluidic cues.细胞在综合化学和流体线索下作为三进制逻辑门决定迁移方向。
Lab Chip. 2023 Feb 14;23(4):631-644. doi: 10.1039/d2lc00807f.
一种胰腺导管腺癌异质浸润的仿生肿瘤模型。
Small. 2020 Mar;16(10):e1905500. doi: 10.1002/smll.201905500. Epub 2020 Jan 30.
4
Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution.胰腺癌的转录表型是由肿瘤进化过程中的基因组事件驱动的。
Nat Genet. 2020 Feb;52(2):231-240. doi: 10.1038/s41588-019-0566-9. Epub 2020 Jan 13.
5
Epithelial to mesenchymal plasticity and differential response to therapies in pancreatic ductal adenocarcinoma.胰腺导管腺癌中的上皮-间质可塑性及对治疗的不同反应
Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):26835-26845. doi: 10.1073/pnas.1914915116. Epub 2019 Dec 16.
6
Co-culture of functionally enriched cancer stem-like cells and cancer-associated fibroblasts for single-cell whole transcriptome analysis.功能富集的肿瘤干细胞样细胞和肿瘤相关成纤维细胞的共培养用于单细胞全转录组分析。
Integr Biol (Camb). 2019 Dec 31;11(9):353-361. doi: 10.1093/intbio/zyz029.
7
A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling.一种仿生胰腺癌芯片揭示了通过 ALK7 信号进行的内皮细胞消融。
Sci Adv. 2019 Aug 28;5(8):eaav6789. doi: 10.1126/sciadv.aav6789. eCollection 2019 Aug.
8
Tumor spheroid-on-a-chip: a standardized microfluidic culture platform for investigating tumor angiogenesis.肿瘤球体芯片：用于研究肿瘤血管生成的标准化微流控培养平台。
Lab Chip. 2019 Sep 7;19(17):2822-2833. doi: 10.1039/c9lc00140a. Epub 2019 Jul 30.
9
Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer.基质微环境塑造胰腺癌的肿瘤内结构。
Cell. 2019 Jun 27;178(1):160-175.e27. doi: 10.1016/j.cell.2019.05.012. Epub 2019 May 30.
10
A tumorsphere model of glioblastoma multiforme with intratumoral heterogeneity for quantitative analysis of cellular migration and drug response.多形性胶质母细胞瘤肿瘤球体模型，具有肿瘤内异质性，用于定量分析细胞迁移和药物反应。
Exp Cell Res. 2019 Jun 1;379(1):73-82. doi: 10.1016/j.yexcr.2019.03.031. Epub 2019 Mar 25.