Cancer cell heterogeneity: an essay

Heterogeneity in Cancer: Cancer Stem Cells versus Clonal Evolution by Mark Shackleton, Elsa Quintana, Eric R Fearon and Sean J Morrison, Cell 2009(Sep 4); 138(5): 822-29. [FriendFeed entry][Full text]. Summary:

The identification and characterization of cancer stem cells might lead to more effective treatments for some cancers by focusing therapy on the most malignant cells. To achieve this goal it will be necessary to determine which cancers follow a cancer stem cell model and which do not, to address technical issues related to tumorigenesis assays, and to test the extent to which cancer cell heterogeneity arises from genetic versus epigenetic differences.

Presentation on miRNA replacement therapy

Mirna Therapeutics Presents Data at Keystone Symposium on MicroRNA and Cancer, Business Wire, June 15, 2009 [Entry in FriendFeed]. Excerpt:

The expression of miR-34 is reduced in a variety of cancers as well as in cancer stem cells, suggesting that miR-Rx34 may have broad applicability as an anti-cancer agent in miRNA replacement strategies.

About promyelocytic leukaemia protein (PML)

Stemming out of a new PML era? A review by Paolo Salomoni, Cell Death Differ 2009(Jun 12) [Epub ahead of print][Entry in FriendFeed] PubMed Abstract:

The promyelocytic leukaemia protein PML is a growth and tumour suppressor inactivated in acute promyelocytic leukaemia (APL). Recent evidence indicates that PML plays a tumour-suppressive role in cancer of multiple histological origins. However, it is only very recently that PML growth-suppressive functions have been implicated in regulating physiological processes and tissue homoeostasis. In particular, it has been shown that PML is one of the key cell-cycle regulators controlling stem cell function in multiple tissues, from the blood to the brain. As a consequence, PML loss has an impact on tissue development and maintenance of stem cell pools. In addition, new data suggest that PML regulates self-renewal in cancer stem cells. Finally, the oncogenic fusion protein PML/RARalpha, contrary to the conventional view, appears to hijack growth-suppressive pathways to promote transformation of haematopoietic stem cells and to maintain the APL stem cell niche. Overall, these findings not only represent a change in paradigm in the field of PML/APL research, but also contribute to the understanding of fundamental mechanisms underlying stem cell function in vivo. The main objective of this review is to critically discuss the very recent literature on the role of PML in stem cells and tumour-initiating cells. Ultimately, it aims to propose new avenues of investigation.Cell Death and Differentiation advance online publication, 12 June 2009; doi:10.1038/cdd.2009.63.

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).

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.