Researchers find new kind of prostate SC in mice

New Type Of Adult Stem Cells Found In Prostate May Be Involved In Cancer Development, ScienceDaily, September 10, 2009. Excerpts:

The new study may resolve this conundrum because the newly discovered adult stem cells are also luminal cells. "Previous research suggested that prostate cancer originates from basal stem cells, and that during cancer formation these cells differentiate into luminal cells," said Dr. Shen. "Instead, CARNs may represent a luminal origin for prostate cancer" [CARNs stands for "castration-resistant Nkx3.1-expressing cells"].

And indeed, the researchers found that CARNs in mice can give rise to prostate cancers, after the cells lose the activity of PTEN, a gene that is frequently mutated in human prostate cancers.

See also: New Progenitor Cell in Mice Can Cause Prostate Cancer, Michael Smith, Medpage Today, September 9, 2009; Researchers find prostate cancer stem cell, Reuters, September 9, 2009.

These news items are about the publication: A luminal epithelial stem cell that is a cell of origin for prostate cancer by Xi Wang and 9 co-authors, including Michael M Shen, Nature 2009(Sep 9) [Epub ahead of print][PubMed Citation].

Comment: These CSCs were found in mice, and "it is unclear whether CARNs exist in the normal human prostate and if human prostate cancers can originate from these CARNs" (see last paragraph of the Medpage Today article).

Found via: Two Studies Make Promising Advances in Prostate Cancer Research, Denis Cummings, FindingDulcinea, September 10, 2009.

Rak gene helps protect PTEN tumor suppressor

News release: Gene Prevents Destruction of Tumor Suppressor in Breast Cancer, The University of Texas M. D. Anderson Cancer Center, April 6, 2009. Excerpt from the end of the release:

"Recently, we found that Rak can prevent spontaneous DNA damage and has a critical role in suppressing cancer stem cells," he [Shiaw-Yih Lin] said. "So, we will expand our research efforts toward determining how Rak helps to maintain genomic integrity."

Other versions of this news release: Rak gene helps protect tumor suppressor in breast cancer, News-Medical.Net, April 7, 2009; Gene Helps Protect Tumor Suppressor In Breast Cancer, ScienceDaily, April 6, 2009.

The news releases are based on this article: Rak functions as a tumor suppressor by regulating PTEN protein stability and function by Eun-Kyoung Yim and 10 co-authors, including Shiaw-Yih Lin, Cancer Cell 2009(Apr 7); 15(4): 304-14 [PubMed Citation][Full text].

Minireview: PTEN, SC , and CSC

PTEN, stem cells, and cancer stem cells by Reginald Hill and Hong Wu, J Biol Chem 2008(Dec 30) [Epub ahead of print]. [Accepted Manuscript] PubMed Abstract:

Like normal stem cells, "cancer stem cells" (CSCs) have the capacity for indefinite proliferation and generation of new cancerous tissues through self-renewal and differentiation. Among the major intracellular signaling pathways, Wnt, Shh, and Notch are known to be important in regulating normal stem cell activities and their alterations are associated with tumorigenesis. It has become clear recently that phosphatase and tensin homologue (PTEN) is also critical for stem cell maintenance and that PTEN loss can cause the development of CSCs and ultimately tumorigenesis.

Liver progenitor cell population with CSC phenotype

Expansion of CD133 expressing liver cancer stem cells in liver specific PTEN deleted mice by C Bart Rountree, Wei Ding, Lina He, Bangyan Stiles, Stem Cells 2008(Nov 13). [Epub ahead of print]. PubMed Abstract:

Background: PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a lipid phosphatase that regulates mitogenic signaling pathways, and deficiency of PTEN results in cell proliferation, survival, and malignancy. Murine liver specific Pten deletion models develop liver malignancy by twelve months of age. Using this model, we describe a population of CD133+ liver cancer stem cells isolated during the chronic injury phase of disease progression and before primary carcinoma formation. Methods: We performed immunohistochemistry and flow cytometry isolation using livers from 3 and 6-monthold Pten(loxp/loxp); Alb-Cre+ mice (Mutants) and controls. CD133+CD45- non-parenchymal (NP) cells were analyzed for gene expression profile and protein levels. Single CD133+CD45- oval cells were isolated for clonal expansion and tumor analysis. Cultured and freshly isolated liver CD133+CD45- and CD133-CD45- NP cells were injected into immune-deficient and immune-competent mice. Results: In Mutant mice, the NP fraction increases in CD133+CD45- cells in 3 and 6-month Pten deleted animals compared to controls. Clone lines expanded from single CD133+CD45- cells demonstrated consistent liver progenitor cell phenotype, with bi-lineage gene expression of hepatocyte and cholangiocyte markers. CD133+ cells from expanded clone lines formed robust tumors in immune-deficient and immune-competent mice. Furthermore, freshly isolated CD133+CD45- NP liver cells from six month-old Mutants formed tumors invivo, and CD133-CD45- NP cells did not. Consistent with a cancer stem cell phenotype, CD133+ cells demonstrate resistance to chemotherapy agents compared to CD133- cells. Conclusions: CD133+CD45- non-parenchymal cells from chronic injury Pten(loxp/loxp); Alb-Cre+ mice represent a bi-potent liver progenitor cell population with cancer stem cell phenotype.

The full text of this article is openly accessible [PDF].

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.