Modelling the brain tumour microenvironment in 3D using tailored hydrogels

癌细胞周围的基质在疾病进展中起着重要作用，相互信号传导使细胞能够从基质中“读取”信息，并使肿瘤细胞重新设计其基质环境。目前的模型使用动物或商业基质制备物在实验室中进行2D培养。这两种选择都不能准确地复制人体基质中复杂的蛋白质和糖的组成。最近，我们开发了一种基于简单短肽基序的全合成、高度可重复的水凝胶。癌细胞以及其他细胞类型可以沿着包裹在凝胶中并在实验室中轻松生长。这些凝胶可以很容易地用相关的蛋白质/肽或聚糖功能化，以创建定制的基质环境，模拟肿瘤发展的组织。至少有50种不同类型的原发性脑肿瘤。某些类型的肿瘤只发生在大脑的一个非常特定的部分，在一个确定的发展阶段，这表明一个允许的微环境短暂存在。除此之外，只有某些类型的原发性肿瘤（例如肺转移到大脑）。我们将创建定制的基质环境来测试这一假设，并确定限制或确实促进肿瘤生长和进展的关键因素/细胞相互作用。

The matrix surrounding cancer cells plays a significant role in disease progression, with reciprocal signalling enabling cells to 'read' messages from the matrix and for tumour cells to re-engineer their matrix environment. Current models use animals or commercial matrix preparations in 2D culture in the lab. Neither option accurately replicates the complex protein and sugar compositions of human matrix.Recently, we developed a fully synthetic, highly reproducible hydrogel based on a simple short peptide motif. Cancer cells, along with other cell types, can be encapsulated in the gels and easily grown in the lab. These gels can be easily functionalized with relevant proteins/peptides or glycans to create bespoke matrix environments, to mimic the tissues in which tumours develop.There are at least 50 distinct types of primary brain tumours. With some tumour types only occurring in a very specific part of the brain at a defined developmental stage suggesting a permissive microenvironment briefly exists. In addition to this, only some types of primary tumours e.g. lung metastasize to the brain.We will create bespoke matrix environments to test this hypothesis and identify the key factors/cellular interactions that limit or indeed promote tumour growth and progression.