实验室培育的肿瘤可能帮助找到阻断肿瘤生长的方法

Lab-grown tumour could hold key to cancer

位于伦敦的Barts癌症研究所的一个研究小组正在从零开始构建一个肿瘤的生长，以改善治疗。

作者：罗宾·麦克基《观察家科学》编辑。

Frances Balkwill教授说她关于肿瘤发展的理论是有争议的。

英国科学家已经开始研究一个革命性的建筑项目:从其基本的生物成分中构建一个肿瘤。

虽然建造而不是摧毁一个肿瘤的想法似乎是有悖常理的，但其目的是了解癌症是如何发展的以及它们是如何通过身体扩散的。为了实现这一雄心勃勃的目标，位于伦敦的Barts癌症研究所的研究人员从卵巢癌患者身上提取了组织，并将这些样本剥离到其组成成分中。现在他们用这些来试图从头开始重建肿瘤。

这个名为CanBuild的项目, 通过来自欧盟和英国癌症研究的178万英镑的拨款资助, 旨在提供洞察癌症发展的复杂过程。研究人员说，在这项研究，可以改进肿瘤治疗。

该工程动工于2013年，预计将在两年内完工。不过，初步结果将于7月初公布，届时将在伦敦举行的皇家学会夏季展览中，特别展出该团队的研究。

“人们普遍认为肿瘤是一种简单的恶性肿瘤细胞，”项目负责人弗兰·巴尔克威尔教授说。但事实并非如此。只有大约一半构成肿瘤的细胞实际上是恶性细胞。在肿瘤中发现的其他非恶性细胞包括免疫细胞，如巨噬细胞、淋巴细胞、成纤维细胞、内皮细胞、脂肪细胞等。一个肿瘤实际上是一个完整的器官，更确切地说，是一个器官，由于它所获得的额外细胞，它获得了自己的血管和结构。

至关重要的是，这些额外的细胞实际上并不是由肿瘤本身生长的。它们从周围的健康组织中分离出来。

然后，在它们被肿瘤招募之后，它们被它腐化了，以帮助它发展。“这些细胞已经变成了黑暗的一面，”Balkwill说。

当细胞内的基因开关——例如，来自肺部或乳房组织的细胞——被激活时，就会引发癌症，导致它不受控制地分裂。细胞内的故障安全机制通常会阻止或抑制这种肆无忌惮的自我复制过程。然而，在某些情况下，这些防御机制失效，肿瘤开始形成。

Balkwill说:“一开始，当肿瘤仅仅由一些恶性细胞组成时，基因就会在细胞核内打开。”“这些基因引导细胞制造出被称为细胞因子和趋化因子的化学物质，而这些化学物质负责招募所有其他细胞组成肿瘤。”

被这些化学信使吸引到不断增长的肿瘤的细胞中，有成纤维细胞，它们制造出提供组织结构的基质。其他的包括淋巴细胞，树突状细胞，自然杀伤细胞和巨噬细胞，它们通常参与人体的免疫防御。通过将这些细胞转化为其病因，肿瘤抑制了机体的免疫反应，从而得以逃脱监测和攻击。

此外，促进血管发展的细胞也被纳入正在形成的肿瘤中，为新产生的肿瘤提供能量来源，以及为自身创造结构的物质，并为免疫攻击提供防御。

Balkwill认为这个复杂的过程是由最初的恶性细胞驱动的。她坚持认为，这不是肿瘤首先出现的组织的固有属性。“我承认这个想法是有争议的，但我相信它是正确的，”她补充道。

Balkwill和她的同事们分离出了制造肿瘤的各种各样的积木，现在正试图把它们重新组合起来，创造出一个。“我们已经对卵巢肿瘤进行了分析，并分析了它们的成分，现在我们试图将这些碎片拼在一起，从而产生一个肿瘤。”本质上，我们已经拆解了一个肿瘤，现在我们要尝试重建一个肿瘤。

“关键的一点是，我们将在实验室中进行一项研究——我们将在实验室中进行研究——我们了解了很多关于特定肿瘤的知识，我们希望我们能够找到阻断或扰乱肿瘤在人体的形成过程的方法。”

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参考文献

Lab-grown tumour could hold key to cancer

A research team at Barts Cancer Institute in London is constructing a cancerous growth from scratch to improve treatment

Robin McKie Observer science editor

Professor Frances Balkwill says her theory about the development of tumours is controversial.

British scientists have started work on a revolutionary construction project: building a tumour from its basic biological components.

While the idea of building rather than destroying a tumour might seem perverse, the aim is to understand how cancers develop and how they spread through the body. To achieve this ambitious goal, the researchers based at Barts Cancer Institute in London have taken tissue from ovarian cancer patients and stripped these samples down to their constituent components. Now they are using these to try to rebuild a tumour from scratch.

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The project, known as CanBuild, has been funded through a £1.78m grant from the European Union and Cancer Research UK and is intended to provide insights into the complex process by which cancers develop. In the wake of this work, improved tumour treatments could be created, say researchers.

Work on CanBuild began in 2013 and is expected to be completed in two years. However, preliminary results will be unveiled early in July in a special display of the team’s work that will form a part of the Royal Society’s summer exhibition in London.

“It is common to think of cancers as being simple balls of malignant cells,” said project leader Prof Fran Balkwill. “But that is not the case. Only about half the cells that make up a tumour are actually cancerous. Other non-malignant cells that are found in a tumour include immune cells such as macrophages, lymphocytes, fibroblasts, endothelial cells, fat cells and many more. A tumour is really an entire organ – a rogue organ, more precisely – that has acquired its own blood vessels and structure thanks to the additional cells it has acquired.”

Crucially, these additional cells are not actually grown by the cancers themselves. They are suborned from surrounding healthy tissue.

Then, after they are recruited by the cancer, they are corrupted by it in order to help it develop. “These are cells that have been turned to the dark side,” said Balkwill.

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A cancer is triggered when genetic switches within a cell – for example, a cell from a lung or from breast tissue –are turned on, causing it to divide uncontrollably. Fail-safe mechanisms within the cell normally stop or hold back this process of unbridled self-replication. However, on occasions, these defence mechanisms fail and a tumour begins to form.

“At the very start, when the tumour only consists of a few malignant cells, genes are turned on inside their nuclei,” said Balkwill. “These genes direct the cells to make chemicals that are known as cytokines and chemokines – and these chemicals are responsible for recruiting all the other cells that go to make up a tumour.”

Among the cells that are drawn into the growing cancer by these chemical messengers are fibroblasts which manufacture the matrix that provides tissue with its structure. Others include lymphocytes, dendritic cells, natural killer cells and macrophages which are normally involved in the body’s immune defences. By subverting these cells to its cause, the cancer suppresses the body’s immune responses and so manages to escape detection and attack.

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In addition, cells that facilitate the development of blood vessels are drawn into the emerging cancer, supplying the newly created cancer with a source of energy – as well as material to create a structure for itself and to provide defences against immune attack.

Balkwill believes that this whole complex process is driven by the initial malignant cell. It is not an inherent property of the tissue in which the tumour first arises, she insists. “The idea is controversial, I admit, but I believe it is right,” she added.

Having isolated the various building blocks that are suborned to make a tumour, Balkwill and her colleagues are now trying to put them back together to create one. “We have taken ovarian tumours and analysed their composition and now we are trying to put together those pieces in order to create one tumour. Essentially we have deconstructed a tumour and now we are going to try to reconstruct one.

“The crucial point is that in putting one together – which we will do in the laboratory – we learn so much about a particular tumour, we hope that we will be able to find ways of blocking or disrupting that process in the human body.”

https://www.theguardian.com/science/2016/jul/02/cancer-lab-grown-tumour-research-treatment