Molecular link connecting breast cancer SCs with normal SCs

Stanford scientists find common trigger in cancer and normal stem cell reproduction, EurekAlert, August 6, 2009. First paragraph:

Researchers at Stanford University School of Medicine have discovered, for the first time, a common molecular pathway that is used by both normal stem cells and cancer stem cells when they reproduce themselves.

See also: Common Trigger In Cancer And Normal Stem Cell Reproduction Found, ScienceDaily, August 7, 2009. About the article:

Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells by Yohei Shimono and 14 co-authors, including Michael F Clarke, Cell 2009(Aug 7); 138(3): 592-603. [FriendFeed entry][PubMed Citation]. Summary:

Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells invitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs invivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.

For a commentary, see the latter part of: Breast cancer stem cells resemble healthy stem cells, resist chemotherapy by Monya Baker, The Niche, August 10, 2009.

On CSC and therapeutic sensitivity studies

If cancer stem cells are resistant to current therapies, what’s next? by Paola Marcato‌, Cheryl A Dean‌, Carman A Giacomantonio‌ and Patrick WK Lee‌, Future Oncol 2009(Aug); 5(6): 747-50. [Twitter entry][FriendFeed entry][PubMed Citation]. Excerpts from the final portion of this Editorial:

Thus far, oncolytic viruses as a class of novel cancer therapeutics appear to kill CSCs with the same efficiency as non-CSCs [references]. Therefore, the characteristics that make CSCs resistant to current therapies do not limit the ability of the viral-based therapies to infect and kill these cells. Of further interest is the possibility of engineering oncolytic viruses to specifically kill tumor cells that express CSC markers.

We conclude that with increasing evidence that CSCs are potent initiators of cancer and have an intrinsic resistance to current therapies, scientists and clinicians will need to rethink traditional end points, such as tumor regression, as the major indicator of the efficacy of anticancer therapies, new and old.

CSC, brain cancer and the STAT3 gene

STAT3 Gene Regulates Cancer Stem Cells in Brain Cancer, News Release, Tufts University, August 10, 2009. First paragraph:

In a study published online in advance of print in Stem Cells, Tufts researchers report that the STAT3 gene regulates cancer stem cells in brain cancer. Cancer stem cells have many characteristics of stem cells and are thought to be the cells that drive tumor formation. The researchers report that STAT3 could become a target for cancer therapy, specifically in Glioblastoma multiforme (GBM), a type of malignant and aggressive brain tumor.

See also: [Newswise][Insciences][EurekAlert][Medical News Today].

These News Releases are about this article: STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells by Maureen M Sherry and 4 co-authors, including Brent H Cochran, Stem Cells 2009(Aug 5) [Epub ahead of print]. [PubMed Citation].

MicroRNA-181 and liver cancer

Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells by Junfang Ji and 15 co-authors, including Carlo M Croce and Xin Wei Wang, Hepatology 2009(Aug); 50(2): 472-80. [PubMed Abstract][Full text of author manuscript, available in PMC 2009(Aug 5)].

See also: EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features by Taro Yamashita and 15 co-authors, including Xin Wei Wang, Gastroenterology 2009(Mar); 136(3): 1012-24.e4 [Epub 2008(Dec 5)]. [PubMed Abstract].

And: New kids on the block: Diagnostic and prognostic microRNAs in hepatocellular carcinoma by Junfang Ji and Xin Wei Wang, Cancer Biology & Therapy 2009(Sep 15); 8(18) [Forthcoming].

Gene signatures in residual breast cancers after conventional therapy

Gene Signature of Breast Cancer Stem Cells Revealed, Genetic Engineering & Biotechnology News, August 4, 2009. First paragraph:

A consortium of researchers have identified the gene expression patterns of breast cancer stem cells that remain post treatment with either chemotherapy or antihormone treatments. They report that this gene signature differs from those linked to the bulk of epithelial cells in the tumor.

Based on: Gene signature for cancer stem cells may provide drug targets, Glenna Picton, News Release, Baylor College of Medicine, August 4, 2009.

See also: Gene signature for cancer stem cells may provide drug targets, Science Centric, August 4, 2009. First paragraph:

A subset of tumour cells that remain after a woman with breast cancer undergoes treatment with either anti-cancer or anti-hormone therapy shows a 'gene signature' that could be used to define targets for developing new drugs against the disease, said a consortium of researchers led by Baylor College of Medicine. The report appears in the current issue of the Proceedings of the National Academy of Sciences.

The report referred to in the above excerpt is an Open Access publication: Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features by Chad J Creighton and 22 co-authors, including Michael T Lewis, Jeffrey M Rosen and Jenny C Chang, Proc Natl Acad Sci USA 2009(Aug 3). [Epub ahead of print].[Abstract][Early version of OA full text].

Human bladder tumor-initiating cells

Scientists discover bladder cancer stem cell by Krista Conger, News Release, Stanford University, August 3, 2009. First paragraph:

Researchers at Stanford's School of Medicine have identified the first human bladder cancer stem cell and revealed how it works to escape the body's natural defenses.

See also: Stanford scientists discover bladder cancer stem cell, EuekAlert, August 3, 2009. And: Scientists Discover Bladder Cancer Stem Cell, ScienceDaily, August 4, 2009. [FriendFeed entry].

The news releases are based on this Open Access publication: Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells by Keith Syson Chan and 11 co-authors, including Irving L Weissman, Proc Natl Acad Sci USA 2009(Aug 4) [Epub ahead of print]. [Abstract][Early version of OA full text].

A post about another recent publication from Stanford: Leukemia SC cloak themselves to avoid detection (July 28, 2009).

Luminal progenitor cells in breast cancer

A new progenitor cell population in breast cancer, Nature Asia-Pacific, August 3, 2009. First paragraph:

Some breast cancers are thought to arise from mammary stem cells that mutate, but a study published in this week's Nature Medicine indicates that luminal cells that line the mammary ducts may also be tumor progenitors.

This Research Highlight is based on the publication: Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers by Elgene Lim and 20 co-authors, including kConFab, Jane E Visvader and Geoffrey J Lindeman, Nat Med 2009(Aug 2) [Epub ahead of print]. Final sentence of the PubMed Abstract:

Our findings suggest that an aberrant luminal progenitor population is a target for transformation in BRCA1-associated basal tumors.

See also: Breast cancer discovery heralds diagnosis hope by Nick Miller, theage.com.au, August 3, 2009. Excerpt:

The breakthrough research came from the study of a unique collection of breast cancer tissue donated by Australian women.

And: Stem cell 'daughters' lead to breast cancer, EurekAlert, August 2, 2009. [FriendFeed entry]. Note to anyone who might find this title confusing: The word 'daughters' refers to cells that are produced by stem cells, not to the 'daughters' of patients!