Tailored biomaterial to mimic cell-cell interactions and enhance circulating tumour cell culture

体内的大多数细胞都被称为细胞外基质（ECM）的低聚糖和蛋白质网络所包围。ECM有很多作用，为组织提供力量，促进细胞存活，细胞分化，并在细胞从一个地方移动到另一个地方时引导细胞。细胞外基质的特定成分，如胶原蛋白或透明质酸可用于治疗，但单独这些成分只能提供完整复杂环境特性的一小部分。我们正在应对综合系统的挑战，这些系统既易于制作，又融入更多ECM的多样性和复杂性，从而更好地模仿其活动。在这项工作中，我们将建立特定的化学反应，利用高亲和力的蛋白质相互作用，从自然界设计，在理想的条件下修饰ECM聚合物透明质酸细胞生长。通过将信号分子固定在细胞通常会在体内遇到的透明质酸上，我们将提供一种刺激，使活细胞对环境保持敏感，否则活细胞在隔离状态下会很快死亡。特别是，在人造的静态环境中，如用于细胞生长和研究的环境中，保持循环肿瘤细胞的存活，仍然是一个巨大的挑战。循环肿瘤细胞从原发肿瘤中释放出来，在肿瘤发展的每个阶段都存在于血液中。发现这些细胞为早期癌症诊断提供了重要的机会，因此治疗可能会更成功。有了这些可用于测试的细胞，还可以根据病人的情况改进癌症治疗的选择。每个人的癌症在药物敏感性上都有差异，这对于应用个性化药物至关重要。然而，通常一份血液样本只能提供5到50个循环肿瘤细胞——不足以进行药物测试。我们将生成简单的聚合物，并将其整合到我们的基质中，这些聚合物能够模拟循环肿瘤细胞通常接收到的信号，并监测癌细胞如何对这些信号做出反应和分裂。从长远来看，循环肿瘤细胞存活率的提高将大大增加从单个血液样本中获得的信息，这既有助于了解癌症，也有助于快速确定对每个个体最有效的药物治疗。

Most cells in the body are surrounded by a network of oligosaccharides and protein called the extracellular matrix (ECM). The ECM has a huge number of roles, providing strength to a tissue, as well as promoting cell survival, cell differentiation and guiding cells as cells move from one place to another. Specific components of the extracellular matrix, such as collagen or hyaluronic acid may be used therapeutically, but individually these components only provide a fraction of the properties of the full complex environment. We are addressing the challenge of synthesising systems that are simple to make yet incorporating more of the diversity and complexity of the ECM and therefore better mimicking its activities. In this work we will establish specific chemical reactions, using high affinity protein interactions engineered from nature, to modify the ECM polymer hyaluronic acid under conditions ideal for cell growth. By anchoring signalling molecules onto hyaluronic acid which cells would normally encounter in the body, we will provide a stimulus to keep alive cell types sensitive to their environment alive cells which would die quickly in isolation otherwise. In particular, keeping alive circulating tumour cells in artificial static environment such as those used to grow and study cells, is still a big challenge. Circulating tumour cells are released from the primary tumour and are present in the blood at every stage of tumour development. Finding these cells gives an important opportunity for early cancer diagnosis and so treatment is likely to be more successful. Having these cells available for tests would also allow improved selection of cancer treatment depending on the patient. Each individual's cancer has differences in drug sensitivity, which are critical to uncover for applying personalized medicine. Yet often a blood sample only gives 5 to 50 circulating tumour cells - not enough for drug testing. We will generate and incorporate in our matrix simple polymers able to mimic signals normally received by the circulating tumour cells and monitor how cancer cells respond and divide in response to these signals. In the long-term, augmented survival of circulating tumour cells will greatly increase the information that can be obtained from a single blood sample, both for understanding cancer and for rapidly identifying drug treatments that will be most effective for each individual.