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乳腺癌原代细胞系为药物筛选和基础研究提供癌症新模型
Establishment of primary breast cancer cell line as new model for drug screening and basic research
- 中国癌症杂志 2024年34卷第6期 页码：561-570
- 作者机构：
1. 贵州医科大学附属医院病理科，贵州 贵阳 550004
2. 贵州医科大学附属医院乳腺外科，贵州 贵阳 550004
3. 贵州医科大学附属医院急诊骨科，贵州 贵阳 550004
4. 贵州医科大学附属医院临床医学研究中心，贵州 贵阳 550004
5. 中国医学科学院基础医学研究所 北京协和医学院基础学院，中国医学科学院组织工程研究中心，干细胞新药研发及临床转化研究北京市重点实验室（BZ0381），北京 100005
- 作者简介：
[ "郝 弦（ORCID：0009-0000-7499-0789 ），硕士研究生。" ]
赵春华（ORCID：0000-0002-4609-8424），教授，E-mail: zhaochunhua@vip.163.com。豆晓伟（ORCID：0000-0002-9601-7047），副研究员，E-mail: douxw@gmc.edu.cn。
- 基金信息：贵州省科技计划项目重点项目(ZK[2023]重点033)
DOI：10.19401/j.cnki.1007-3639.2024.06.004
中图分类号： R737.9收稿：2024-05-02，
修回：2024-06-07，
纸质出版：2024-06-30
- 稿件说明：
移动端阅览
郝弦, 黄建军, 杨文秀, 等. 乳腺癌原代细胞系为药物筛选和基础研究提供癌症新模型[J]. 中国癌症杂志, 2024,34(6):561-570.
Xian HAO, Jianjun HUANG, Wenxiu YANG, et al. Establishment of primary breast cancer cell line as new model for drug screening and basic research[J]. China Oncology, 2024, 34(6): 561-570.
郝弦, 黄建军, 杨文秀, 等. 乳腺癌原代细胞系为药物筛选和基础研究提供癌症新模型[J]. 中国癌症杂志, 2024,34(6):561-570. DOI： 10.19401/j.cnki.1007-3639.2024.06.004.
Xian HAO, Jianjun HUANG, Wenxiu YANG, et al. Establishment of primary breast cancer cell line as new model for drug screening and basic research[J]. China Oncology, 2024, 34(6): 561-570. DOI： 10.19401/j.cnki.1007-3639.2024.06.004.
摘要
背景和目的：
2016年美国国家癌症研究所（National Cancer Institute，NCI）宣布不再使用NCI-60细胞系进行药物筛选，提示传统的肿瘤细胞系失去作为药物研发和基础研究工具的价值。NCI-60细胞“退休”原因是基于癌症细胞系和动物的实验结果没有在临床试验中获得对应的预期，导致绝大部分潜在药物临床试验失败。癌症细胞系失去价值归因于肿瘤细胞经过长期培养后，其增殖和转移等主要生物学行为和与之有关的关键蛋白质系统发生了根本改变，已不能代表患者的真实癌症特征。现阶段需要创立一种来源于患者新鲜癌症组织和具有清晰临床背景的新癌症模型。本研究旨在为药物研发和基础研究建立经济的患者来源的可以无限传代的乳腺癌原代细胞系。
方法：
乳腺癌组织在贵州医科大学附属医院乳腺外科收集。肿瘤组织样本收集得到贵州医科大学附属医院伦理委员会批准（伦理编号：2022伦理第313号），收集和使用肿瘤组织均遵守赫尔辛基宣言，患者的乳腺癌组织消化分离后在BCMI培养基中培养，待乳腺癌细胞增殖到一定数量时更换成DMEM培养基。乳腺癌细胞经短串联重复序列（short tandem repeat，STR）检测确定细胞特异性遗传学标志和来源。克隆形成实验和动物实验分析乳腺癌原代细胞系形成肿瘤的能力。
结果：
成功建立了6种乳腺癌原代细胞系。他们具有清晰的临床病理学特征，包括病理学标志性分子检测、临床诊断、治疗方案和结果以及确定的预后结果。STR检测确定了6种乳腺癌原代细胞系特异性遗传标志和确定了该细胞系的来源。克隆形成实验和动物移植实验说明乳腺癌原代细胞系增殖能力显著大于传统乳腺癌细胞系，二者在形成肿瘤能力方面存在明显的差异。
结论：
构建的6种乳腺癌原代细胞系为乳腺癌药物研发和基础研究提供了新的癌症模型。
Abstract
Background and purpose:
In 2016 the National Cancer Institute (NCI) decided stopping to use NCI-60 cell lines for drug screening
suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research. The reason for NCI-60 cells 'retirement' was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials. Since the major cancer behaviors
such as proliferation and metastasis
are fundamentally altered with long-term culture
the tumor cell lines are not representative of the characteristics of can
cer in patients. Currently
scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past. Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.
Methods:
Breast cancer tissues were collected in the Department of Breast Surgery
Affiliated Hospital of Guizhou Medical University. The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University (approval number: 2022 ethics No. 313)
and the collection and use of tumor tissues complied with the Declaration of Helsinki. The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium. After the cells proliferated
the media were replaced with DEME medium. Cell line STR genotyping was done to determine cell-specific genetic markers and identification. Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.
Results:
We created 6 primary breast cancer cell lines. The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features
clinical diagnosis
therapeutic regimens
clinical effectiveness and prognostic outcomes. The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines. Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.
Conclusion:
We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.
关键词
Keywords
references
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