Wednesday, December 3, 2008

Tumorigenic cells not rare in human melanoma

Efficient tumour formation by single human melanoma cells by Elsa Quintana and 5 co-authors, including Sean J Morrison, Nature 2008(Dec 4); 456(7222): 593-8. Abstract:
A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells (0.1–0.0001%) form tumours when transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, the extent to which NOD/SCID mice underestimate the frequency of tumorigenic human cancer cells has been uncertain. Here we show that modified xenotransplantation assay conditions, including the use of more highly immunocompromised NOD/SCID interleukin-2 receptor gamma chain null (Il2rg -/-) mice, can increase the detection of tumorigenic melanoma cells by several orders of magnitude. In limiting dilution assays, approximately 25% of unselected melanoma cells from 12 different patients, including cells from primary and metastatic melanomas obtained directly from patients, formed tumours under these more permissive conditions. In single-cell transplants, an average of 27% of unselected melanoma cells from four different patients formed tumours. Modifications to xenotransplantation assays can therefore dramatically increase the detectable frequency of tumorigenic cells, demonstrating that they are common in some human cancers.
See also: U-M scientists probe limits of 'cancer stem-cell model'; Melanoma, the deadliest skin cancer, does not fit the model, News Release, University of Michigan, December 3, 2008.


  1. See also: Cancer stem cells: Here, there, everywhere? by Connie J Eaves, Nature 2008(Dec 4); 456(7222), 581-2 [PubMed Citation]. Excerpt:

    Can every tumour cell propagate human cancers or is this property exclusive to an elite subset? Findings are divided. The latest set shows that — depending on circumstances — both perspectives can be correct.

  2. A publicly-accessible News Feature: Cancer stem cells, becoming common, Monya Baker, Nature Reports Stem Cells, December 3, 2008. Excerpt:

    [William] Matsui found that patients with tumours whose invasive margin contained this marker [ALDH, an enzyme highly expressed in blood-forming and neural stem cells] survived, on average, four months less than those whose tumours did not. Other groups have also reported a correlation with stem cell markers or gene expression and shorter life expectancy.[9, 10, 11].

    One could argue that, from a translational-research perspective, associations with clinical outcome are the most meaningful assessments that should be made.

  3. Another relevant post: Cancer stem cells: controversies and misconceptions, Monya Baker, The Niche: the stem cell blog, December 18, 2008. Excerpts:

    Nature recently published a paper by Sean Morrison and others finding that melanoma stem cells are not rare and that standard assays to identify tumorigenic cells fail to detect a large portion of them. This prompted [some correspondence].....

    Here, we publish that correspondence along with replies from David Taussig, which describes evidence for that cancer stem cell hypothesis, including his own evidence that leukemia-initiating cells are less than 1 in 100 cells. Finally, a reply by John Dick and colleagues says that the effects described by Taussig do not apply to a key leukemogenic cell marker and goes on to describe misconceptions about the cancer stem cell model.

  4. See also: Tweaking and Testing Cancer Stem Cell Models, Spotlight section, NCI Cancer Bulletin 2008(Dec 16); 5(25). Excerpt:

    Tumors do not grow in a vacuum, she [Dr. Connie Eaves] continued, and few grow in the complete absence of host immune components. "So it is not yet clear that going to extraordinary lengths to promote human tumor growth in a mouse will ultimately be the best test of what propagates a tumor in a person," she said.

  5. For two recent publicly accessible reviews about CSC and melanoma [written prior to the publication of Efficient tumour formation by single human melanoma cells in Nature 2008(Dec 4); 456(7222): 593-8], see: OA reviews about cancer stem cells and melanoma, Be openly accessible or be obscure, December 28, 2008.

  6. Another commentary: Cancer stem cells: Common as muck by Safia Ali Danovi, Nature Reviews Cancer 2009(Jan); 9(1), 6-7. Excerpt: Recent data from Sean Morrison and colleagues provide ammunition for the naysayers. [There's toll-free access to the full text (free registration is required)].

  7. See also this post: The CSC hypothesis: recalling some history, Cancer Stem Cell News, December 30, 2008.