3D Microenvironments to Investigate Pancreatic Cancer Cell Migration

用于研究胰腺癌细胞迁移的 3D 微环境

• 批准号: 1944415
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1944415
• 关键词: 3D; Microenvironments; Investigate; Pancreatic; Cancer

Pancreatic cancer is among the most deadly and metastatic cancers. Pancreatic tumours have an unusually stiff and dense stroma that might serve as both a barrier and promoter of metastasis. This project will develop tools to investigate the molecular mechanisms of pancreatic cancer cell invasion and metastasis, combining bioengineering and cell biology to gain insights into how pancreatic cancer cells invade and metastasise. The complexity of native stroma prevents detailed molecular analysis, but bioengineered substrates offer a chance to manipulate the matrix in a well-defined way to determine molecular mechanisms. Hydrogels are networks of hydrated, cross-linked polymers which are powerful models of the extracellular matrix often used in cell biology; therefore they provide a promising substrate to study cancer biology. The ability to incorporate cell adhesive and protease degradable sequences, and growth factors with defined localisations and densities while controlling the pore size and mechanical properties of the substrate is a strong advantage over natural 3D systems which are difficult to define.Since the tumour microenvironment is 3D and complex, we will engineer 3D hydrogels with controlled properties such as matrix stiffness, integrin binding sites and bound growth factors. These parameters will be varied systematically and a panel of pancreatic cancer cells will be analysed for their ability to migrate in 3D, and detailed imaging of the stroma and invading cells will be performed. We aim to gain insight into which properties of the matrix promote the spread of pancreatic cancer with the hope of targeting these for future therapies.

胰腺癌是最致命和最转移的癌症之一。胰腺肿瘤具有异常坚硬和致密的间质，可能既是转移的屏障，也是转移的促进器。该项目将开发工具来研究胰腺癌细胞侵袭和转移的分子机制，将生物工程和细胞生物学结合起来，以深入了解胰腺癌细胞如何侵袭和转移。天然基质的复杂性阻碍了详细的分子分析，但生物工程底物提供了以明确定义的方式操纵基质以确定分子机制的机会。水凝胶是一种水合的、交联的聚合物网络，是细胞生物学中常用的细胞外基质的强大模型，因此它们为癌症生物学的研究提供了一种很有前途的底物。与难以定义的自然3D系统相比，能够整合具有特定定位和密度的细胞黏附和蛋白酶降解序列和生长因子，同时控制底物的孔大小和机械性能是一个强大的优势。由于肿瘤微环境是3D和复杂的，我们将设计具有可控特性的3D水凝胶，如基质硬度、整合素结合位置和结合生长因子。这些参数将被系统地改变，一组胰腺癌细胞将被分析其在3D中的迁移能力，并将对基质和侵袭细胞进行详细的成像。我们的目标是深入了解基质的哪些特性促进胰腺癌的扩散，并希望将这些特性作为未来治疗的靶点。