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

转移是癌细胞从肿瘤部位（原发部位）转移到继发性癌症形成的身体其他部位（转移部位）。在乳腺癌中，转移是导致几乎所有死亡的原因，每年在英国有超过11000人死亡，因此迫切需要更多地了解导致疾病传播和进展到绝症的一系列复杂事件。为了使乳腺癌转移，癌细胞需要适应，这样它们才能离开原发部位，在血液中存活，当它们移动到新的部位时，最重要的是，这样它们才能在新的环境中生存，最常见的是骨骼，肺，肝脏和大脑。对癌细胞适应同样重要的是需要发生在转移部位的变化，这被描述为“种子和土壤”假说——你可以在地上撒很多种子，但如果土壤不合适，植物就不会生长，相比之下，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。我们认为原发肿瘤在准备癌细胞到达的转移部位方面起着重要作用-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在生命系统中缺乏控制，迄今为止进展有限。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转移部位之间的相互作用。这个系统是基于Arti Ahluwalia教授开发的一个系统，她在比萨大学用这个系统来模拟腹部的组织相互作用和新陈代谢。我们将调整这个模型用于曼彻斯特的乳腺癌转移模型，并询问乳腺癌细胞向远处组织发送什么信号，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。

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.