Replacing in vivo models with the Quasi vivo system to investigate metastatic site priming by tumour cells.

用准体内系统代替体内模型来研究肿瘤细胞引发的转移部位。

• 批准号: NC/W000792/1
• 负责人: Hannah Harrison
• 金额: $ 9.6万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FW000792%2F1
• 关键词: Replacing; vivo; models; Quasi; system

Metastasis is the movement of cancer cells away from the site of a tumour (the primary site) to other areas of the body where a secondary cancer forms (the metastatic site). In breast cancer, metastasis is responsible for nearly all deaths from the disease, more than 11,000 people each year in the UK, and so there is an urgent need to learn more about the complex series of events which leads to disease spread and progression to terminal disease.In order for a breast cancer to metastasise the cancer cells need to adapt so that they can leave the primary site, survive within the blood stream whilst they travel to the new site and, most importantly, so that they can live in a new environment, most commonly the bone, lung, liver and brain. Equally important to the cancer cell adaptations are the changes that need to occur at the metastatic site, and this has been described as the "seed and soil" hypothesis - you can scatter many seeds on the ground but if the soil is not suitable the plant will not grow, comparably many tumour cells may move around the body but if they do not find a suitable site, they will not form a secondary tumour. We believe that the primary tumour plays an important role in preparing the metastatic site for cancer cell arrival - it makes the soil suitable for the seed. To test this hypothesis studies have previously been carried out in animals aiming to identify the signals which are driving these changes. Due to the complexity of these models and the lack of control in a living system progress to date has been limited. Here we propose a novel laboratory-based, cell line system which we can use to model the interactions between the breast cancer cells and the likely sites of metastasis. This system is based on one which Professor Arti Ahluwalia has developed and which she uses in Pisa to model tissue interactions and metabolism in the abdomen for example. We will adapt this model for use in breast cancer metastasis modelling for use in Manchester and ask what signals the breast cancer cells are sending to the distant tissues to prime them for cancer cell arrival. If we can find ways to block these signals, we will reduce secondary tumour formation and the associated patient mortality.

转移是癌细胞从肿瘤部位（原发部位）移动到身体的其他区域，在那里形成继发性癌症（转移部位）。在乳腺癌中，转移是几乎所有死于该疾病的原因，在英国每年有超过11，000人死亡，因此迫切需要更多地了解导致疾病扩散和发展为晚期疾病的复杂系列事件。为了使乳腺癌转移，癌细胞需要适应，以便它们能够离开原发部位，当它们迁移到新的位置时，它们可以在血液中存活，最重要的是，它们可以在新的环境中生存，最常见的是骨骼，肺，肝脏和大脑。与癌细胞适应性同样重要的是需要在转移部位发生的变化，这被描述为“种子和土壤”假设-你可以在地面上散布许多种子，但如果土壤不适合，植物就不会生长，许多肿瘤细胞可能会在身体周围移动，但如果它们找不到合适的位置，它们就不会形成继发性肿瘤。我们认为，原发性肿瘤在为癌细胞到达转移部位做准备方面发挥着重要作用-它使土壤适合种子。为了验证这一假设，之前已经在动物身上进行了研究，旨在识别驱动这些变化的信号。由于这些模型的复杂性和缺乏对生命系统的控制，迄今为止的进展是有限的。在这里，我们提出了一种新的基于实验室的细胞系系统，我们可以用它来模拟乳腺癌细胞和可能的转移部位之间的相互作用。该系统基于阿尔蒂阿卢瓦利亚教授开发的一个系统，她在比萨使用该系统来模拟腹部的组织相互作用和代谢。我们将调整这个模型用于在曼彻斯特使用的乳腺癌转移建模，并询问乳腺癌细胞向远处组织发送什么信号，以使它们为癌细胞的到来做好准备。如果我们能找到阻断这些信号的方法，我们将减少继发性肿瘤的形成和相关的患者死亡率。