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癌症研究中最热门的一个理论是，疾病可能因为许多不好的癌症干细胞蔓延，新发现显示黑色素瘤的这些增殖者细胞比过去报告的还要常见，而需要重新评估。
过去的研究显示，100万个黑色素瘤细胞中仅有1个具有变性的能力，表现出造成新肿瘤的不受抑制增殖力。然而，一项以不同检验系统的新研究结果显示，有四分之一的黑色素瘤细胞是具有演变成肿瘤的潜力的。
这项新发现是12月4日自然期刊上的封面故事。
研究者们评论，细胞演变成肿瘤的潜力，在人类癌症中是很常见或是罕见的问题，对于治疗具有基本的应用。
他们写到，如果具有肿瘤潜力的细胞代表少数族群，就由证据支持癌症干细胞模式，接着这可能研发出改善的癌症治疗，仅杀死这些癌症干细胞，而不是所有的癌症细胞，包括很大部分团块之非具致癌潜力的癌症细胞。然而，如果这些干细胞是常见的，接着，仅针对这少部分的细胞族群可能无法更有效地治疗癌症。
【目前存在的证据并不能应用在黑色素瘤上】
作者解释，这项最新的研究，由密西根大学的研究者进行，使用一种新的检验系统来侦测老鼠移植物中具有致癌潜力的癌症细胞。过去的研究使用NOD/SCID老鼠模式，这个老鼠模式的免疫力严重受损，但并非完全没有功能；虽然这样的老鼠模式缺乏T与B细胞，他们仍然有自然杀手细胞，这些细胞会攻击且破坏许多移植的癌细胞。
因此，研究者们研发了一种新模式（没有介白素2迦玛受体NOD/SCID老鼠模式），其中，自然杀手细胞、T与B细胞被排除。在这些更宽容的状况下，来自12位不同病患大约有25%未经选择的黑色素细胞会形成肿瘤。研究者报告，这些包括直接取自病患原发性与转移性黑色素瘤的细胞。他附带表示，在单一细胞移植，来自4位不同患者的黑色素瘤细胞，有24%形成肿瘤。
研究者们相信，这结果之间的差异，以及那些之前得到的，可以以自然杀手细胞解释，这些自然杀手细胞会璀毁过去老鼠模式中许多移植肿瘤细胞。主要研究者安纳堡密西根生命科学机构干细胞生物学中心主任Sean Morrison博士表示，过去那个检验是根据忽略了大部分会增殖成肿瘤的细胞。
研究者在一篇新闻稿中表示，这项新发现并非癌症细胞模式失效。Morrison博士在声明中评论，癌症干细胞确实存在，但他们可能比估计的更加常见。
Morrison博士认为，癌症干细胞模式最终将会拦截部分癌症；但是其他癌症，例如黑色素瘤，可能并不会照着一个癌症干细胞模式走。这个领域在花更多时间去最佳化使用于侦测癌症细胞的模式之前，将需要被重新评估。
密西根大学综合癌症研究中心多专业黑色素瘤计划主任Timothy Johnson医师指出，人们现在把癌症干细胞模式看作进展性黑色素瘤中，研发拯救生命新疗法的一个令人兴奋的新资源。不幸的，我们的结果显示黑色素瘤并非完全跟随着这个模式。
Johnson医师附带表示，因此我们将会重新导引我们的科学研究，并且继续专注在人类黑色素瘤生成的基础生物演变过程。当我们追求进展性黑色素瘤的新疗法，我们将必须考虑大部分的癌症细胞是需要被杀掉的。
研究者表示没有相关资金上的往来。
Cancer Stem-Cell Model May Need to Be Reassessed
By Zosia Chustecka
Medscape Medical News
One of the hottest new theories in cancer — that the disease is propagated by a handful of rogue cancer stem cells — might need to be reassessed for many cancers in light of new findings with melanoma that suggest that these propagator cells are more common than has previously been supposed.
Previous studies have suggested that only 1 in 1?million melanoma cells have the ability to run wild, exhibiting the kind of unchecked proliferation that leads to new tumors. However, a new study conducted with a different assay system suggests that as many as 1 in 4 melanoma cells are tumorigenic.
The new finding is the cover article of the December 4 issue of Nature.
"The question of whether cells with tumorigenic potential are common or rare within human cancers has fundamental implications for therapy," the researchers comment.
If tumorigenic cells represent small minority populations, as suggested by evidence supporting the cancer stem-cell model, then it could be possible to develop improved anticancer therapies that would kill only these cancer stem cells, rather than all of the cancer, including the large bulk of nontumorigenic cancer cells. However, if these cancer stem cells are common, then it will not be possible to treat cancer more effectively by focusing on small minority subpopulations of cells, they write.
Existing Model Does Not Apply to Melanoma
The latest study, conducted by researchers at the University of Michigan, used a new assay system to detect tumorigenic cancer cells in mouse transplants. Previous studies have used the NOD/SCID mouse model in which the immune system is severely impaired but not completely inoperative; although these mice lack T and B cells, they still possess natural killer cells, which attack and destroy many of the transplanted cancer cells, the researchers explain.
Hence, the researchers developed a new model (NOD/SCID mice lacking the interleukin-2 gamma receptor), in which the natural killer cells and the T and B cells were eliminated. Under these more permissive conditions, approximately 25% of unselected melanoma cells from 12 different patients formed tumors, the researchers report. These included cells from primary and metastatic melanomas obtained directly from the patients. In single-cell transplants, an average of 27% of unselected melanoma cells from 4 different patients formed tumors, they add.
The researchers believe that the difference between their results and those obtained previously can be explained by the natural killer cells, which wiped out many of the transplanted cancer cells in the older mouse model. "The assay on which the field is based misses most of the cancer cells that can proliferate to form tumors," said lead researcher Sean Morrison, PhD, director of the Center for Stem Cell Biology at the University of Michigan Life Sciences Institute, in Ann Arbor.
The new finding does not invalidate the cancer stem-cell model, the researchers emphasized in a press release. Cancer stem cells likely do exist, but they are "probably much more common than people have been estimating," Dr. Morrison commented in the statement.
"I think the cancer stem-cell model will, in the end, hold up for some cancers," Dr. Morrison said. "But other cancers, like melanoma, probably won't follow a cancer stem-cell model at all. The field will have to be reassessed after more time is spent optimizing the methods used to detect cancer stem cells."
"People were looking to the cancer stem-cell model as an exciting new source for the development of life-saving cures for advanced melanoma," commented coauthor Timothy Johnson, MD, director of the Multidisciplinary Melanoma Program at the University of Michigan Comprehensive Cancer Center. "Unfortunately, our results show that melanoma does not strictly follow this model."
"So we'll need to redirect our scientific efforts and remain focused on the fundamental biological processes underlying the growth of melanomas in humans," Dr. Johnson added. "As we pursue new treatments for advanced melanoma, we'll have to consider that a high proportion of cancer cells may need to be killed."
The researchers have disclosed no relevant financial relationships.
Nature 2008;456:593-598.