Cancer and stem cells
癌与干细胞
A strand apart
一链之差
Jan 14th 2010 | SAN FRANCISCO
From The Economist print edition
More evidence that tumours, like healthy organs, grow from stem cells
更多证据显示，肿瘤同健康器官一样，由干细胞发育而成。
THE notion that tumours are chaotic masses of anarchic cells has been falling by the wayside recently. Many researchers now think, by contrast, that cancers actually resemble normal, well-regulated organs in several important ways. One of these is that they are believed to have a small population of stem cells which keep them going when other cells die or are killed off. The existence of such cancer stem cells is still a matter of debate. But this week the discussion may have taken an important turn. Brid Ryan, Sharon Pine and Curtis Harris, of America’s National Cancer Institute, reported that some lung-cancer cells do, indeed, seem to behave like stem cells during the process of cell division.
认为肿瘤是一堆杂乱无章的异常细胞的观点，最近已经遭到摒弃。许多研究者认为，恰恰相反，肿瘤在几个重要方面都与正常有序的器官相似。其中一个方面就是，人们认为肿瘤内也有一定数量的干细胞，这些干细胞使得肿瘤能够在其他细胞死亡或被消灭的情况下还能继续生长。这种肿瘤干细胞是否存在，目前仍存在争议。但是，这种争论在本周或许已经发生重大变化。美国国家癌症研究所布里德·瑞安、沙农·派恩和柯蒂斯·哈里斯报道，一些肺癌细胞在细胞分裂过程中确实表现得像干细胞。
Unlike normal cells, stem cells can divide in two different ways. They may do so symmetrically, thereby producing identical daughter cells, each of which resembles the mother cell. Or they may do so asymmetrically, and give rise to two very different daughters. In such cases, one of the daughters is identical to the original stem cell, while the other takes on new characteristics and can then differentiate into whatever cell type the tissue it inhabits requires.
与普通细胞不同，干细胞分裂有两种途径。干细胞可进行对称分裂，从而产生完全相同的子细胞，每个子细胞与母细胞相似。干细胞也可进行不对称分裂，产生两个完全不同的子细胞。在第二种情况下，其中一个子细胞与原始干细胞相同，而另一个子细胞则具有了新特征，并能分化成所在组织需要的任何细胞类型。
During asymmetrical divisions, some stem cells take an extra step to preserve the integrity of their DNA. Part of the process of cell division involves the duplication of a cell’s chromosomes, so that each daughter can have a full set of these strands of DNA. Instead of sending old and new chromosomes into the daughter cells at random, the dividing stem cell carefully shuttles all of its old chromosomes into the daughter that remains a stem cell. The newly synthesised DNA, which may contain errors, is put into the daughter that is destined to differentiate. That way, any mutations which have arisen during DNA replication will not affect the all-important stem cell population.
为了保留DNA的完整性，一些干细胞的不对称分裂过程要多经历一个步骤。细胞分裂过程包含细胞染色体的复制，以使每个子细胞具有完整的DNA链。分裂的干细胞并不是将原来的染色体和新生成的染色体随机分配给子细胞，而是精心地将原来的染色体封装到仍充当干细胞的子细胞中。可能含有错误片段的新合成DNA则被分配给分化子细胞。通过这种方式，DNA复制过程中出现的任何错误都不会影响到极为重要的干细胞群。
Until now, the main evidence supporting the cancer-stem-cell hypothesis has been the observation that many different types of tumour contain a small group of cells, identifiable by special types of protein found on their surfaces, that can form new tumours with high efficiency. (By contrast, the cells that comprise the bulk of most tumours lack these surface proteins and are poor at creating new tumours.)
到目前为止，支持肿瘤干细胞假说的主要证据是发现许多不同类型的肿瘤都含有能高效率生成新肿瘤的一小群细胞，通过细胞表面的特殊类型的蛋白质能够识别这些细胞。（与之相比，组成大部分肿瘤主体的细胞没有这种表面蛋白，生成新肿瘤的能力也很弱。）
Dr Ryan, Dr Pine and Dr Harris reasoned that if such cells really are stem cells then they should be able to undergo both symmetrical and asymmetrical divisions, just like the stem cells in healthy tissue. They looked in samples taken directly from patients with lung cancer, and also in lung-cancer cells from laboratory cultures. In both cases, when they grew the cells in the presence of a chemical that infiltrates newly synthesised DNA, they could see that the unlabelled template strands of DNA went into one daughter cell and the new strands went to the other. Moreover, the daughter that retained the old DNA also retained the cell-surface proteins that mark the putative cancer stem cells.
瑞安、派恩和哈里斯三位博士推论认为，若此类细胞真是干细胞，它们就应该像健康组织中的干细胞一样，既能进行对称分裂，又能进行不对称分裂。他们观察了直接取自肺癌患者的样本，也观察了实验室培养的肺癌细胞。他们在培养基中添加能渗入新合成DNA的化学试剂，结果，两种情况下都观察到未标记的模板DNA链进入了一个子细胞，而新合成的DNA链进入了另一个子细胞。而且，保留了原来DNA的子细胞同时也保留了假定的肿瘤干细胞特有的细胞表面蛋白。
The team, who presented their results at a joint meeting of the American Association for Cancer Research and the International Association for the Study of Lung Cancer in Coronado, California, this week, are now investigating whether their putative cancer stem cells are more resistant than run-of-the-mill cancer cells to chemotherapy or radiation, as research on other putative stem cells has suggested. What they do know is that when they grow these cells in culture, they can push them toward either asymmetrical or symmetrical division by controlling the density of cells and the amount of oxygen available. If they can find a similar way to control the cells’ fate in patients’ tumours, they may have opened a new avenue for cancer therapy.
本周，在加利福尼亚州科罗纳多举行的美国癌症研究学会和国际肺癌研究学会联合会议上，该小组公布了他们的研究结果。他们现在正在研究假定的肿瘤干细胞是否像其他假定干细胞上的研究显示的一样，比普通癌细胞更耐化疗及放疗。目前他们所知道的是，人工培养这些细胞时，可以通过控制细胞密度和氧通量来强制细胞进行不对称分裂或是对称分裂。如果能找到类似的方法来控制患者肿瘤细胞，或许，他们就开启了癌症治疗的新途径。
译者：hddmail126