Cell of origin for human prostate cancer

Scientists at UCLA find cell of origin for human prostate cancer by Kim Irwin, UCLA Newsroom, July 29, 2010. Excerpts:

"Certainly, the dominant thought is that human prostate cancer arose from the luminal cells because the cancers had more features resembling luminal cells," said Witte, senior author of the study and a Howard Hughes Medical Institute Investigator. "But we were able to start with a basal cell and induce human prostate cancer, and now, as we go forward, this gives us a place to look in understanding the sequence of genetic events that initiates prostate cancer and defining the cell-signaling pathways that may be at work fueling the malignancy, helping us to potentially uncover new targets for therapy."

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The new human-in-mouse model system developed in the study was created by taking healthy human prostate tissue that will induce cancer once it is placed in mice, instead of taking malignant tissue that is already cancerous and implanting it. This model can now be used to evaluate the effectiveness of new types of therapeutics. By using defined genetic events to activate specific signaling pathways, researchers can more easily compare therapeutic efficacy. The new model, by deconstructing tissue and then reconstructing it, also will aid in analyzing how the cells change during cancer progression.

This news release is based on the publication: Identification of a Cell of Origin for Human Prostate Cancer by Andrew S Goldstein and 5 co-authors, including Owen N Witte, Science 2010(Jul 30); 329(5991): 568-71. [PubMed citation][FriendFeed entry][Twitter trackbacks via Topsy].

Prostate CSCs sensitive to gamma-tocotrienol?

Gamma-Tocotrienol Kills Prostate Cancer Stem Cells, PRNewswire, July 25, 2010. Excerpt:

The scientists found that low doses of gamma-tocotrienol cause apoptosis in the prostate cancer stem cells and suppress their colony formation capability. This results in a lower prostate cancer stem cell population (as defined by the protein markers CD133 and CD44). Further tests in mice models were conducted, where mice implanted with hormonal refractory prostate cancer cells were given gamma-tocotrienol orally. The results showed that gamma- tocotrienol not only reduced tumour size formed, but also decreased the incidence rate of tumour formation by 75%, as compared to the control group of mice, which had 100% tumour formation. These results strongly suggest that gamma-tocotrienol could be developed for prostate cancer prevention and treatment.

The news release by Davos Life Science is based on the publication:

Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population by Sze Ue Luk and 11 co-authors, including Ming-Tat Ling, Int J Cancer 2010(Jul 8) [Epub ahead of print][PubMed citation].

Comment:

See also a relevant patent application: (WO/2010/047663) Use of Tocotrienol Composition for the Prevention of Cancer.
Publication Date: 29.04.2010
Applicants: DAVOS LIFE SCIENCE PTE. LTD. [SG/SG]; 16 Tuas South Street 5 Singapore 637795 (SG) (All Except US).
LING, Ming Tat [CN/AU]; (AU) (US Only).
YAP, Wei Ney [MY/SG]; (SG) (US Only).
WONG, Yong Chuan [MY/CN]; (CN) (US Only).
YAP, Yee Leng, Daniel [MY/SG]; (SG) (US Only).

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.

SC markers invention

United States Patent Application 20090012024, Anne Collins, Norman Maitland, Steven Bryce, January 8, 2009. [See also: Stem Cell Markers and Stem cell markers]. Abstract:

We disclose gene markers of stem cells, typically prostate stem cells, and in particular cancer stem cells, for example prostate cancer stem cells; therapeutic agents and diagnostic assays based on said stem cell genes; and including screening assays to identify therapeutic agents.

Excerpt:

[0030]We have conducted gene array analysis to identify genes that are characteristic of cancer stem cells which show an up regulation when compared to control stem cell samples from normal or benign stem cell populations. We herein disclose these genes and their use in the identification of therapeutic agents useful in the treatment of cancer, in particular prostate cancer, and in the development of diagnostic assays for the detection of the early on set of tumour cell growth. The present disclosure relates to the identification of cancer stem cell specific genes.

An earlier Patent Application: 20080233640, Norman James Maitland, Anne Collins, September 25, 2008. [See also: Prostate Stem Cell and Prostate stem cell]. Abstract:

We describe a method for the isolation of prostate stem cells, typically prostate stem cells which express CD 133 antigen; stem cells and cancer stem cells isolated by the method and their use.

Two recent publications from this research group [not publicly accessible]:

Inflammation as the primary aetiological agent of human prostate cancer: a stem cell connection? Norman J Maitland, Anne T Collins, J Cell Biochem 2008(Nov 1); 105(4): 931-9 [PubMed Citation].

Prostate cancer stem cells: a new target for therapy, Norman J Maitland, Anne T Collins, J Clin Oncol 2008(Jun 10); 26(17): 2862-70 [PubMed Citation].

A recent news item:

Investors back their belief in biotech company by Bernard Ginns, Yorkshire Post, January 20, 2009. Excerpts:

Pro-Cure's expertise is in the culture, isolation, handling and gene profiling of human prostate cancer stem cells. It is working with a number of big pharmaceutical firms in this burgeoning area.

Its management team includes Professor Norman Maitland, director of Yorkshire Cancer Research and professor of molecular biology at the University of York, who is regarded as one of the world leaders in his field.

The website for Pro-Cure Therapeutics includes a page about the Management Team.