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

体内的大多数细胞都被一种叫做细胞外基质(ECM)的寡糖和蛋白质网络所包围。细胞外基质有大量的作用，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，如胶原或透明质酸，可以用于治疗，但单独而言，这些成分只提供整个复杂环境的一小部分特性。我们正在应对这样的挑战，即合成既易于制造又包含更多ECM的多样性和复杂性的系统，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，使用从自然中设计的高亲和力蛋白质相互作用，在理想的细胞生长条件下修饰ECM聚合物透明质酸。通过将信号分子锚定在细胞通常在体内遇到的透明质酸上，我们将提供一种刺激，以保持活细胞类型对其环境敏感的活细胞，否则细胞将在隔离中迅速死亡。特别是，在人工静态环境中保持循环中的肿瘤细胞存活，例如用于生长和研究细胞的环境，仍然是一个巨大的挑战。循环中的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。发现这些细胞为癌症的早期诊断提供了一个重要的机会，因此治疗可能会更成功。让这些细胞用于测试也将允许根据患者的不同改进癌症治疗的选择。每个人的癌症对药物的敏感性都不同，这对于发现应用个性化药物至关重要。然而，一份血液样本通常只提供5到50个循环中的肿瘤细胞--不足以进行药物测试。我们将产生简单的聚合物并将其加入我们的基质中，这些聚合物能够模拟循环中的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，提高循环中肿瘤细胞的存活率将极大地增加从单个血液样本中获得的信息，无论是为了了解癌症，还是为了快速确定对每个人最有效的药物治疗。

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.