Three-dimensional breast cancer tumor models based on natural hydrogels: a review

Yan SHU; Bing LI; Hailin MA; Jiaqi LIU; Yuen Yee CHENG; Xiangqin LI; Tianqing LIU; Chuwei YANG; Xiao MA; Kedong SONG

doi:10.1631/jzus.B2300840;10.1631/jzus.B2300840

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Review | Updated：2024-09-20

Three-dimensional breast cancer tumor models based on natural hydrogels: a review
Three-dimensional breast cancer tumor models based on natural hydrogels: a review
基于天然水凝胶的三维乳腺癌肿瘤模型研究进展
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 9, Pages: 736-755(2024)
Affiliations：

1.State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China
2.Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, NSW 2007, Australia
3.Emergency Center, the Second Hospital of Dalian Medical University, Dalian 116023, China
4.Department of Anesthesia, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
Funds：
DOI：10.1631/jzus.B2300840;10.1631/jzus.B2300840
CLC：
CSTR：
Published： 15 September 2024 ，

Received： 06 December 2023 ，

Revised： 20 February 2024 ，
Accepted：

疏艳,李冰,马海林等.基于天然水凝胶的三维乳腺癌肿瘤模型研究进展[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(09):736-755.

Yan SHU, Bing LI, Hailin MA, et al. Three-dimensional breast cancer tumor models based on natural hydrogels: a review. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(9):736-755(2024)
疏艳,李冰,马海林等.基于天然水凝胶的三维乳腺癌肿瘤模型研究进展[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(09):736-755. DOI： 10.1631/jzus.B2300840;10.1631/jzus.B2300840.

Yan SHU, Bing LI, Hailin MA, et al. Three-dimensional breast cancer tumor models based on natural hydrogels: a review. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(9):736-755(2024) DOI： 10.1631/jzus.B2300840;10.1631/jzus.B2300840.

摘要

乳腺癌是女性最常见的癌症，同时也是世界范围内致死率最高的癌症之一。根据肿瘤组织的分布部位，乳腺癌可分为浸润性乳腺癌和非浸润性乳腺癌。浸润性乳腺癌中的癌细胞通过免疫系统或体循环穿过乳房到达身体的不同部位，形成转移性乳腺癌（耐药性和远处转移是乳腺癌致死的最主要原因），因此针对乳腺癌的研究受到了研究人员的广泛关注。通过组织工程方法体外构建的肿瘤模型是研究癌症机制和筛选抗癌药物的常用工具。肿瘤微环境由癌细胞和各种类型的基质细胞组成，包括成纤维细胞、内皮细胞、间充质细胞和嵌入在细胞外基质中的免疫细胞。细胞外基质含有纤维蛋白（例如I、II、III、IV、VI和X型胶原和弹性蛋白）和糖蛋白（例如蛋白聚糖、纤连蛋白和层粘连蛋白）等成分，两者均参与了细胞信号传导和生长因子的结合。目前传统的二维（2D）肿瘤模型因受生长环境限制，往往不能准确再现体内肿瘤组织的异质性和复杂性。因此，近年来，对三维（3D）肿瘤模型的研究逐渐增多，尤其是高精度、高重复性的3D生物打印模型。与2D模型相比，3D环境可以更好地模拟肿瘤微环境中复杂的细胞外基质成分和结构，因此常被用作2D细胞水平实验和动物实验之间的桥梁。此外，脱细胞基质、明胶和海藻酸钠等天然材料因其优异的生物相容性和无免疫排斥性而被广泛用于肿瘤模型的构建。本文综述了组织工程3D肿瘤模型中涉及到的各种天然支架材料及构建方法，以期为乳腺癌领域的研究提供参考。

Abstract

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide. According to the distribution of tumor tissue

breast cancer can be divided into invasive and non-invasive forms. The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body

forming metastatic breast cancer. Drug resistance and distant metastasis are the main causes of death from breast cancer. Research on breast cancer has attracted extensive attention from researchers. In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening. The tumor microenvironment consists of cancer cells and various types of stromal cells

including fibroblasts

endothelial cells

mesenchymal cells

and immune cells embedded in the extracellular matrix. The extracellular matrix contains fibrin proteins (such as types I

III

and X collagen and elastin) and glycoproteins (such as proteoglycan

laminin

and fibronectin)

which are involved in cell signaling and binding of growth factors. The current traditional two-dimensional (2D) tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo. Therefore

in recent years

research on three-dimensional (3D) tumor models has gradually increased

especially 3D bioprinting models with high precision and repeatability. Compared with a 2D model

the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment. Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments. Acellular matrix

gelatin

sodium alginate

and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection. Here

we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models

as a reference for research in the field of breast cancer.

关键词

乳腺癌肿瘤微环境3D肿瘤模型脱细胞基质天然支架材料

Keywords

Breast cancerTumor microenvironment3D tumor modelDecellularized extracellular matrixNatural scaffold materials

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Related Author

Xiping ZHANG

Qiuhui YANG

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Related Institution

The First Clinical Medical College, Shanxi Medical University

Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)

Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences

Department of Oncology, School of Clinical Medicine, Southwest Medical University

School of Medicine, University of Electronic Science and Technology of China

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