Two blog posts about cancer stem cells

Two recent blog posts by Kevin Graham (thanks to Drew Lyall):

1) Meet Kevin Graham: Cancer stem cell researcher, Connecting for Kids, September 19, 2008. Excerpt:

Have you ever heard of tumour stem cells? Did you know that stem cell research is being used to search for a cure for brain tumours? Admittedly, these probably aren’t the first things that jump to your mind when you hear about stem cell research, but that’s exactly why we started this forum.

2) Stem cells, Cancer and Cancer Stem Cells, Connecting for Kids, September 24, 2008. Excerpt:

How do you target a cancer stem cell? This is one of the many ways in which stem cell research is paying off. Early indications are that normal stem cells and cancer stem cells share many of the same cellular processes. Research over the years has compiled an amazing amount of data about how normal stem cells function, information that is now being rapidly applied to cancer stem cells.

The right frame of both posts also includes links to brief profiles of three other stem cell researchers at the Hospital for Sick Children (SickKids) in Toronto: Janet Rossant (mammalian developmental biology and genetics), Peter Dirks (cancer stem cells of brain tumors) and Freda Miller (neuronal stem cells and neuronal growth, survival and apoptosis).

Cancer stem cells in solid tumours: a review

Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Jane E Visvader & Geoffrey J Lindeman, Nature Reviews Cancer 2008(Oct); 8(10): 755-68. Abstract:

Solid tumours are an enormous cancer burden and a major therapeutic challenge. The cancer stem cell (CSC) hypothesis provides an attractive cellular mechanism to account for the therapeutic refractoriness and dormant behaviour exhibited by many of these tumours. There is increasing evidence that diverse solid tumours are hierarchically organized and sustained by a distinct subpopulation of CSCs. Direct evidence for the CSC hypothesis has recently emerged from mouse models of epithelial tumorigenesis, although alternative models of heterogeneity also seem to apply. The clinical relevance of CSCs remains a fundamental issue but preliminary findings indicate that specific targeting may be possible.

This review is currently available free as a special feature to registered visitors to Nature Reviews Cancer. Registration is also free.

PTEN and planarian stem cells

A recent news item: Flatworms can shed new light on cancer, stem cells, News Track India, Sep 18, 2008. Excerpts:

During a study, scientists at the University of Utah and the Forsyth Institute at Harvard found that the flatworm contains a gene highly similar to the human gene PTEN, which is often found to be mutated in cancer cases.

.....

The study has been published in the journal Disease Models and Mechanisms (DMM).

The article is: Planarian PTEN homologs regulate stem cells and regeneration through TOR signaling, Néstor J. Oviedo, Bret J. Pearson, Michael Levin and Alejandro Sánchez Alvarado, Dis. Model. Mech. 2008(Sep 18), doi:10.1242/dmm.000117

The last sentence of the Abstract:

Altogether, our data reveal roles for PTEN in the regulation of planarian stem cells that are strikingly conserved to mammalian models. In addition, our results implicate this protein in the control of stem cell maintenance during the regeneration of complex structures in planarians.

For information about this new journal, see: Disease Models & Mechanisms (DMM), NewJour, August 7, 2008. Excerpt:

To ensure the wide dissemination of all authors' work during the launch year, DMM has made a commitment to provide immediate, unrestricted online access to all articles from Volume 1 on the journal website.

Articles related to pancreatic cancer

Two articles on research related to pancreatic cancer have been published recently. They are:

1) Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer. M Mimeault and S K Batra, Gut 2008(Oct); 57(10): 1456-68. The last two sentences of the Abstract:

The combination of drugs that target the oncogenic elements in pancreatic cancer stem/progenitor cells and their microenvironment, with the conventional chemotherapeutic regimens, could represent promising therapeutic strategies. These novel targeted therapies should lead to the development of more effective treatments of locally advanced and metastatic pancreatic cancers, which remain incurable with current therapies.

At present, only the Abstract is freely-accessible. The publisher (BMJ Publishing Group) makes all archive content older than 12 months freely available to registered users. See: BMJ Journals information centre. See also the SHERPA/RoMEO summary of copyright policies for Gut.

2) An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. G Feldmann and 13 co-authors, Mol Cancer Ther 2008(Sep); 7(9): 2725-35. The last sentence of the Abstract:

Pharmacologic blockade of aberrant Hedgehog signaling might prove to be an effective therapeutic strategy for inhibition of systemic metastases in pancreatic cancer, likely through targeting subsets of cancer cells with tumor-initiating ("cancer stem cell") properties.

At present, only the Abstract is freely-accessible. The publisher (American Association for Cancer Research) makes all articles available free 12 months after the date of initial publication. See: Access to AACR Publications. See also the SHERPA/RoMEO summary of copyright policies for AACR journals.

Searches with Google Scholar

An Advanced Scholar Search, using the key words "cancer stem cell", for articles published in 2008, yielded a list of articles. At the top of the list was: Identification and expansion of the tumorigenic lung cancer stem cell population, by A Eramo and 9 co-authors, Cell Death Differ 2008(Mar); 15(3): 504-14. Unfortunately, at the time this search was done (2008-09-14), only the Abstract was freely accessible.

An analogous advanced search was done (also on 2008-09-14) , again using the key words "cancer stem cell", for articles published in 2007 and 2008. At the top of the list was: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma, by M E Prince and 8 co-authors, Proc Natl Acad Sci U S A 2007 (Jan 16); 104(3): 973-8. This time, the article is freely accessible. As is evident from the PubMed citation, this article has also been archived in the PubMed Central repository.

At the time when this particular search was done, among the first 20 articles listed in the results, 15 were marked with green triangles.

Search results marked in this way are a novel feature. See: Google Scholar starts to flag gratis OA content, by Peter Suber, Open Access News, September 11, 2008.

Peter Suber uses the term "gratis OA" to identify the most basic kind of free online access to the peer-reviewed literature. Price barriers are removed, but permission barriers may still remain. Permission barriers may prevent a range of uses of the freely accessible articles. For example, libraries may be prevented, by licensing terms, from using electronic journals in the same free and full way that they may now use print journals.

At present, as Peter Suber has noted in his post, not all of the search results are correctly marked. However. it's a useful beginning, for those who seek freely accessible versions of articles of interest.

Article in The Economist

There's an article entitled: "Cancer stem cells: The root of all evil?" in The Economist, September 11, 2008. (Thanks to Lisa Willemse, who saw it).

It's an overview of research on cancer stem cells. The last two paragraphs:

If the safety issues can be dealt with—and most researchers think they can—then attacking cancer stem cells really could help patients survive. If, that is, the stem-cell hypothesis is correct.

At the moment, scientists being scientists, few are willing to be anything other than cautious. They have seen too many past cures for cancer vanish in a puff of smoke. The proof needs to come from patients—preferably with them living longer. But if the stem-cell hypothesis is indeed shown to be correct, it will have the great virtue of unifying and simplifying the understanding of what cancer is. And that alone is reason for hope.

Links are also provided, in a frame to the right of the main text, to webpages about scientists named in the article. They are (with links to the webpages used by The Economist): John Dick, Michael Clarke and Max Wicha, Jeremy Rich, William Matsui, Jenny Chang, Robert Weinberg and Craig Jordan.

Added September 13, 2008:

See also "Medicine: Shooting down cancer", The Economist, September 11, 2008. The last two paragraphs:

Like natural selection and germs, the discovery of cancer stem cells illustrates how the most fruitful scientific findings are often not those of individual experiments, however intriguing, but those that organise knowledge into theory. The chemical industry took off within a decade or so of Dmitri Mendeleev’s arrangement of the chemical elements into the periodic table, just as radio communications followed James Clerk Maxwell’s mathematical unification of electricity and magnetism, and antibiotics came after Pasteur and Koch.

With luck, something similar will soon happen in biology in the wake of such things as the Human Genome Project. In retrospect, the discovery of stem cells—cancer stem cells included—may come to be seen as a step in a comprehensive theory of how organisms work. That understanding would be a formidable, if unforeseen, part of the legacy of the war on cancer and an essential part of its mission to save lives.

Cancer spread and stem cells

There's an article, "Breakthroughs seen in cancer spread and stem cells", by Carey Goldberg of The Boston Globe, September 9, 2008. Excerpts from the first page:

Mani and his colleagues at the MIT-affiliated Whitehead Institute found what appears to be a key to metastasis, the insidious process by which cancer spreads throughout the body and often kills. And, in a surprising spinoff, that same discovery also may lead to a relatively safe, simple way to transform normal adult cells into stem cells that could be used to treat other diseases.

The scientists believe their one-step method may avoid the risk of random mutation (and possibly cancer), a stumbling block for therapies based on other recently developed techniques for creating stem cells.

Excerpts from the second page of the same article:

For all his excitement, Weinberg readily acknowledged that Mani's line of investigation has yet to produce a "gold-standard proof" that the stem-like cells are actually stem cells. If their thinking is correct, he said, it should be possible to induce the key metamorphosis in some breast cells of one mouse, place them in another mouse's chest and develop a breast.

The experiment worked once, he said, but his lab has been unable to replicate it and ended up publishing its work in the leading biology journal Cell this May without that crowning proof.

The publication in Cell isn't cited, but it appears to be this one: "The epithelial-mesenchymal transition generates cells with properties of stem cells", by Sendurai A Mani and 14 co-authors, including Robert A Weinberg, Cell 2008(May 16); 133(4): 704-15 [PubMed Abstract]. Unfortunately, the publication isn't freely accessible.

It's been cited by a more recent article (also not freely accessible): "Epithelial-mesenchymal transition and the stem cell phenotype", by Derek C Radisky and Mark A LaBarg, Cell Stem Cell, 2008(Jun 5); 2(6): 511-2 [PubMed Abstract]. The Abstract:

Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire the motile, migratory properties of mesenchymal cells. In a recent issue of Cell, Mani et al. (2008) show that induction of EMT stimulates cultured breast cells to adopt characteristics of stem cells.

A brief excerpt from the full text:

An exciting implication of these results is that there may be a direct relationship between EMT and the phenomenon of CSCs.

Comments on these articles would be welcomed.

CSC in Wikipedia

A couple of new "External links" have recently been added to the Wikipedia article entitled "Cancer stem cell".

A recommendation: those who are actively working on cancer stem cells should monitor this article, and edit it to ensure that it's accurate, up to date, comprehensive, unbiased, and cites credible sources.

There's also an article in Wikipedia entitled "Reliability of Wikipedia". Criteria for assessing the reliability of Wikipedia articles are listed.

Added September 6, 2008: Via WebCite®, the current versions of these Wikipedia articles have been archived.

Cancer stem cell. Wikipedia. URL: http://en.wikipedia.org/wiki/Cancer_stem_cell. Accessed: 2008-09-06. (Archived by WebCite® at http://www.webcitation.org/5ad1588J3)

Reliability of Wikipedia. Wikipedia. URL: http://en.wikipedia.org/wiki/Reliability_of_Wikipedia. Accessed: 2008-09-06. (Archived by WebCite® at http://www.webcitation.org/5ad1fD1V9)

CD133 Expression

There's a commentary, "Capturing cancer stem cells", in Nature Medicine 2008(Aug); 14(8): 814.

It's about reactions to a freely-accessible article entitled: "CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors", by Sergey V Shmelkov and 19 co-authors, in J Clin Invest. 2008(Jun); 118(6): 2111-20. The final sentence of the abstract of this article:

Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133⁺ tumor cells might give rise to the more aggressive CD133^– subset, which is also capable of tumor initiation in NOD/SCID mice.

The commentary in Nature Medicine isn't freely accessible, and has no abstract. It consists mainly of answers to the question: "What do the findings mean for the quest to find and target cancer stem cells?". Answers are provided by Zena Werb, Jeremy Rich and Jeffrey Rosen. Excerpts:

For understanding tumorigenesis and creating therapies, a spectrum of markers may be the answer. [Zena Werb]

No single marker is likely to be absolutely informative, but CD133 has proven repeatedly useful in brain tumor stem cell studies for many research groups. [Jeremy Rich]

[T]he findings do not invalidate previous stem cell work using CD133 antibodies, which recognize a specific epitope that may not be conserved between mice and people. [Jeffrey Rosen]

Other comments about the article by Shmelkov and co-authors, or about the commentary in Nature Medicine, would be welcomed.