癌症水凝胶促进三维肿瘤微环境的产生与评价

IF 0.8 Q4 MATERIALS SCIENCE, BIOMATERIALS
Sheba Goklany, Earl Brown, Lauryn De La Torre, K. Rege
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引用次数: 0

摘要

工程化的三维(3D)细胞培养模型可以加速药物的发现,并在细胞-细胞、细胞-细胞外基质(ECM)和细胞-生物分子相互作用方面带来新的基础见解。现有的用于生成3D肿瘤模型的基于水凝胶或支架的方法不具有显著的可调性,并且对于高通量药物筛选具有有限的可扩展性。我们开发了一种新的水凝胶库,称为阿米卡凝胶,它来源于阿米卡星水合物(AH)和聚乙二醇二缩水甘油醚(PEGDE)的交联。在此,我们描述了Amikagels用于生成乳腺癌症细胞的3D肿瘤微环境(3DTM)的用途。评估这些癌症3DTM的生物学特征,如耐药性和缺氧,并将其与二维(2D)单层培养物的生物学特征进行比较。与各自的2D单层培养物相比,在Amikagels上形成的雌激素受体(ER)阳性乳腺癌症3DTM更休眠。相对于各自的2D培养物,癌症3DTM对米托蒽醌和阿霉素诱导的细胞死亡具有耐药性,米托蒽醌是癌症(包括癌症)常用的化疗药物。在3DTMs中观察到的耐药性与在这些培养物中看到的缺氧相关,但在2D单层培养物中没有。对Mucin 1(MUC1)的抑制导致癌症的2D单层和3DTM的细胞几乎完全死亡,MUC1在缺氧时过表达。ER应激诱导剂和MUC1抑制的组合进一步增强了2D单层和3DTM中的细胞死亡。总之,这项研究表明,Amikagel平台代表了一种在体外生成生理相关3DTM的新技术,可以作为发现耐药乳腺癌症新治疗方法的平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Generation and Evaluation of Hydrogel-Facilitated 3D Tumor Microenvironments of Breast Cancer
Engineered three-dimensional (3D) cell culture models can accelerate drug discovery, and lead to new fundamental insights in cell–cell, cell–extracellular matrix (ECM), and cell–biomolecule interactions. Existing hydrogel or scaffold-based approaches for generating 3D tumor models do not possess significant tunability and possess limited scalability for high throughput drug screening. We have developed a new library of hydrogels, called Amikagels, which are derived from the crosslinking of amikacin hydrate (AH) and poly(ethylene glycol) diglycidyl ether (PEGDE). Here we describe the use of Amikagels for generating 3D tumor microenvironments (3DTMs) of breast cancer cells. Biological characteristics of these breast cancer 3DTMs, such as drug resistance and hypoxia were evaluated and compared to those of two-dimensional (2D) monolayer cultures. Estrogen receptor (ER) positive breast cancer 3DTMs formed on Amikagels were more dormant compared to their respective 2D monolayer cultures. Relative to their respective 2D cultures, breast cancer 3DTMs were resistant to cell death induced by mitoxantrone and doxorubicin, which are commonly used chemotherapeutic drugs in cancer, including breast cancer. The drug resistance seen in 3DTMs was correlated with hypoxia seen in these cultures but not in 2D monolayer cultures. Inhibition of Mucin 1 (MUC1), which is overexpressed in response to hypoxia, resulted in nearly complete cell death of 2D monolayer and 3DTMs of breast cancer. Combination of an ER stress inducer and MUC1 inhibition further enhanced cell death in 2D monolayer and 3DTMs. Taken together, this study shows that the Amikagel platform represents a novel technology for the generation of physiologically relevant 3DTMs in vitro and can serve as a platform to discover novel treatments for drug-resistant breast cancer.
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来源期刊
Nano Life
Nano Life MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
0.70
自引率
12.50%
发文量
14
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