Hydrogel Models with Stiffness Gradients for Interrogating Pancreatic Cancer Cell Fate.

Hydrogel Models with Stiffness Gradients for Interrogating Pancreatic Cancer Cell Fate.
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用于询问胰腺癌细胞命运的具有刚度因子的水凝胶模型。

DOI:
10.3390/bioengineering8030037
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发表时间:
2021-03-13
期刊:
Bioengineering (Basel, Switzerland)
影响因子:
--
通讯作者:
Lin CC
Lin CC
中科院分区:
其他
文献类型:
--
作者:
Chang CY;Lin CC

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胰腺导管腺癌(PDAC)是最常见的胰腺癌类型,在过去的几十年里,患者的存活率只有轻微的改善。PDAC具有高度侵袭性和对化疗的抵抗力,这是因为存在致密的、少血管的纤维组织,该组织由基质细胞和细胞外基质组成。基质细胞增加基质的沉积和交联会导致不同的微环境,这有助于PDAC的发展。在过去的十年里,各种基于水凝胶的体外肿瘤模型已经被开发出来,以模拟和概括PDAC中肿瘤微环境的各个方面。水凝胶化学和工程方面的进展将为发现基质特性如何控制PDAC细胞的生长、迁移、侵袭和耐药性提供新的见解。这些工程化的水凝胶是了解基质性质的变化如何促进癌细胞进展的理想选择,包括趋向性,即细胞对硬度梯度的定向迁移。本文综述了各种基于水凝胶的体外肿瘤模型和产生梯度硬度的方法,以研究PDAC中的迁移和其他肿瘤细胞的命运过程。
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and has seen only modest improvements in patient survival rate over the past few decades. PDAC is highly aggressive and resistant to chemotherapy, owing to the presence of a dense and hypovascularized fibrotic tissue, which is composed of stromal cells and extracellular matrices. Increase deposition and crosslinking of matrices by stromal cells lead to a heterogeneous microenvironment that aids in PDAC development. In the past decade, various hydrogel-based, in vitro tumor models have been developed to mimic and recapitulate aspects of the tumor microenvironment in PDAC. Advances in hydrogel chemistry and engineering should provide a venue for discovering new insights regarding how matrix properties govern PDAC cell growth, migration, invasion, and drug resistance. These engineered hydrogels are ideal for understanding how variation in matrix properties contributes to the progressiveness of cancer cells, including durotaxis, the directional migration of cells in response to a stiffness gradient. This review surveys the various hydrogel-based, in vitro tumor models and the methods to generate gradient stiffness for studying migration and other cancer cell fate processes in PDAC.
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