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."

.....

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].

Disagreement about melanoma CSCs

The Evolving Science of Cancer Stem Cells by Carmen Phillips, NCI Cancer Bulletin 2010(Jul 27); 7(15). Excerpt:

Researchers from Stanford University earlier this month reported in Nature that they had found a marker, CD271, that identified a somewhat unique population of cells that could produce melanoma in highly immunocompromised mice; anywhere from 2.5 percent to 41 percent of cells in their human tumor samples expressed the marker. In additional experiments using similar mice on which human skin was engrafted, only tumor cells with the marker could produce tumors and metastases in the mice. (In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells.)

The publication about CD271 is: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 by Alexander D Boiko and 11 colleagues, Nature 2010(Jul 1); 466(7302): 133-7. [PubMed citation].

Comments: The sentence: "In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells" is noteworthy. Why the difference in results for CD271?

The publication by Boiko and co-authors was cited in a previous post to this blog, "Melanoma-initiating cells identified", dated July 1, 2010.

See also an earlier post to this blog, "Tumorigenic cells not rare in human melanoma", dated December 3, 2008.

Researchers Study CSCs as Therapeutic Targets for Mesothelioma

Researchers Study Cancer Stem Cells as Therapeutic Targets for Mesothelioma, Asbestos.com, July 26, 2010. Excerpt:

In a study published in the International Journal of Oncology, Cortes-Dericks and colleagues tested whether cancer stem cells in malignant pleural mesothelioma express resistance to cisplatin and pemetrexed, two chemotherapy drugs commonly used to treat mesothelioma cancer.

This news item is based on the OA publication entitled: Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed by Lourdes Cortes-Dericks, Giovanni L Carboni, Ralph A Schmid and Golnaz Karoubi, Int J Oncol 2010(Aug); 37(2): 437-44. [PubMed citation].

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).

Irradiating brain's stem cell niche

Irradiating brain's stem cell niche doubles survival time for patients with brain cancers by Kim Irwin, News Release, UCLA Newsroom, July 23, 2010. Excerpt:

Patients with deadly glioblastomas who received high doses of radiation that hit a portion of the brain which harbors neural stem cells had double the progression-free survival time as patients who had lower doses or no radiation targeting the area, a study from the radiation oncology department at UCLA's Jonsson Comprehensive Cancer Center has found.

The news release is based on this OA publication: Irradiation of the Potential Cancer Stem Cell Niches in the Adult Brain Improves Progression-free Survival of Patients with Malignant Glioma by Patrick Evers and 6 co-authors, including Frank Pajonk, BMC Cancer 2010(Jul 21); 10(1):384. [Epub ahead of print][FriendFeed entry].

Comment: On the brain as a model system to study the impact of radiation dose given to stem cell niches. Provides clinical evidence, based on an improvement in progression-free survival, to support the hypothesis that higher radiation doses to neural stem cell (NSC) niches improves patient survival by eradicating CSCs.

More about salinomycin

New mission for salinomycin in cancer by Cord Naujokat, SciTopics, July 15, 2010. Excerpt (in the "continue reading" section):

In addition, a very recent study demonstrates that salinomycin overcomes ATP-binding cassette (ABC) transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like cells (3).

Reference #3: Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells, by Dominik Fuchs and 4 co-authors, including Cord Naujokat, Biochem Biophys Res Commun 2010(Apr 16);394(4): 1098-104 [Epub 2010(Mar 27)][PubMed citation].

Comments: Near the end of this article about salinomycin is the comment that "the investigation of its safety, toxicity, pharmacology and anticancer activity in humans will be a challenge." The author then mentions a preliminary study of "a small cohort of patients with metastatic breast cancer or metastatic head and neck cancers". The results of this preliminary study of the toxicity of salinomycin are summarized. They have not yet been published in the peer-reviewed literature, although a manuscript has been submitted [see reference #4 in the article]. The implication of these preliminary results is that there may be a "therapeutic window" for salinomycin, that is, a drug dosage that yields clinically significant benefits in the absence of excessive toxicity.

For a previous commentary on salinomycin, see: Cancer stem cell breakthrough by Kat Arney, Science Update blog, Cancer Research UK, August 14, 2009. Excerpt:

We need to stress that these were laboratory experiments, and there is no evidence yet that salinomycin can treat cancer in humans. Salinomycin is currently used as an antibiotic for chickens and cows, and it can be toxic or even fatal to humans, causing serious muscle and heart problems.

If there is a "therapeutic window" for salinomycin, it could be a small one, and is likely to vary from one tumor to another.

For a previous post to this blog about salinomycin, see: Identification of selective inhibitors of breast CSCs in mice, August 14, 2009.

Innovative Researcher Vlog

SU2C Innovative Researcher Vlog: Dr. Lawlor (Pt. 3). Video (3:09 min) posted July 13, 2010. Features Elizabeth R Lawlor, University of Michigan, an SU2C Innovative Research Grants Investigator. [About SU2C (Stand Up to Cancer)]. She provides brief comments about her project: "Modeling Ewing Tumor Initiation in Human Neural Crest Stem Cells". How do normal stem cells become cancer stem cells?

An example of a recent (OA) publication from her laboratory: CD133 expression in chemo-resistant Ewing sarcoma cells by
Xiaohua Jiang and 8 co-authors, including Elizabeth R Lawlor,
BMC Cancer 2010(Mar 26); 10: 116. [FriendFeed entry][PubMed citation][Full text via PMC].

Two recent OA articles

Two articles, with Open Access (OA) to the full text (PDF):

Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed, Int J Oncol 2010(Aug); 37(2): 437-44. [PubMed citation].

Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance, Oncol Rep 2010(Aug); 24(2): 501-5. [PubMed citation].

Comment about these journals:

Spandidos Publications publishes six journals. Of these six, two are: International Journal of Oncology (2009 Impact Factor: 2.4) and Oncology Reports (2009 Impact Factor: 1.6). This publisher provides a hybrid open access option. The Information for Authors for all six journals includes, at the bottom of the page, this information: "Should authors prefer or require their article to be freely available as soon as it has been published, they may request open access immediately upon publication for a fee of EUR 450."

CSC news update 2010-07-03

For links to recent news items about CSC, visit this [Topsy] page. An example of a news item that has received attention in the past week:

Cancer Stem Cells Are Not 'One Size Fits All,' Lung Cancer Models Show http://bit.ly/bE9F0V & http://bit.ly/amEkFR. Hashtag: #cancerSC. Posted to Twitter on Fri Jul 02 via TweetDeck

Melanoma-initiating cells identified

Melanoma-initiating cells identified by study by Krista Conger, News release, Stanford School of Medicine, June 30, 2010. Excerpt:

Scientists at the School of Medicine have identified a cancer-initiating cell in human melanomas. The finding is significant because the existence of such a cell in the aggressive skin cancer has been a source of debate. It may also explain why current immunotherapies are largely unsuccessful in preventing disease recurrence in human patients.

The news release is about this publication: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 by Alexander D Boiko and 11 co-authors, including Irving L. Weissman, Nature 2010(Jul 1); 466(7302): 133-7. [FriendFeed entry].

A blog post about this same publication is: Stanford scientists identify a melanoma-initiating cell by Krista Conger, Scope blog, Stanford School of Medicine, June 20, 2010.

See also a commentary about the publication: Cancer stem cells: Invitation to a second round by Peter Dirks, Nature 2010(Jul 1); 466(7302): 40-1. Excerpt:

Boiko et al. study a type of human skin cancer called melanoma and, in particular, cancer cells enriched in a stem-cell marker called CD271. They find that, unlike other cells from the same tumour, CD271-expressing (CD271+) cells could initiate and maintain tumour growth in vivo — an observation consistent with the existence of a melanoma-cell functional hierarchy.

This finding reflects a view different from that of an earlier study by Quintana et al.[3], which demonstrated that, in some cases, as many as 50% of human melanoma cells have tumorigenic potential. In addition, no marker tested identified a tumorigenic subpopulation. The authors[3] concluded that the frequency of cancer cells that can initiate tumorigenesis depends, in part, on the assessment techniques and assays.

Another news item, based on the same publication, is: New hope in fight against skin cancer as deadly 'master cells' are identified for first time, Mail Online, July 1, 2010. Excerpt:

However Dr Alexander Boiko, who made the discovery at Stanford University, said the newly discovered 'stem cells' in advanced skin cancers were often missed by conventional immunotherapy.

'Without wiping out the cells at the root of the cancer, the treatment will fail,' he said.

Comments: Boiko et al. and Dirks suggest reasons why results different from those of Quintana et al. were obtained. One possibility is that the melanomas that the latter authors studied were at an advanced stage. If, as a cancer progresses, more cells acquire the attributes of cancer stem cells, then advanced melanomas may contain very high frequencies of tumorigenic cells.

As Boiko et al. point out in their publication, "The most crucial test of the tumour stem cell hypothesis is that markers or pathways restricted to tumour stem cells can be targets for curative therapies in the patient, which has not yet been done."