Featured Research

from universities, journals, and other organizations

Human melanoma stem cells identified

Date:
August 23, 2012
Source:
University of Colorado Denver
Summary:
Cancer stem cells are defined by three abilities: differentiation, self-renewal and their ability to seed a tumor. These stem cells resist chemotherapy and many researchers posit their role in relapse. A new study shows that melanoma cells with these abilities are marked by the enzyme ALDH, and imagines new therapies to target high-ALDH cells, potentially weeding the body of these most dangerous cancer creators.

Cancer stem cells are defined by three abilities: differentiation, self-renewal and their ability to seed a tumor. These stem cells resist chemotherapy and many researchers posit their role in relapse. A University of Colorado Cancer Center study recently published in the journal Stem Cells, shows that melanoma cells with these abilities are marked by the enzyme ALDH, and imagines new therapies to target high-ALDH cells, potentially weeding the body of these most dangerous cancer creators.

Related Articles


"We've seen ALDH as a stem cell marker in other cancer types, but not in melanoma, and until now its function has been largely unknown," says the paper's senior author, Mayumi Fujita, MD, PhD, investigator at the CU Cancer Center and associate professor in the Department of Dermatology at the CU School of Medicine.

Fujita's group transplanted ALDH+ and ALDH- melanoma cells into animal models, showing the ALDH+ cells were much more powerfully tumorigenic. In the same ALDH+ cells, the group then silenced the gene that creates this protein, finding that with ALDH knocked down, melanoma cells died in cultures and lost their ability to form tumors in animal models. In cell cultures, silencing this ALDH gene also sensitized melanoma cells to existing chemotherapies. When the group explored human tumor samples, they found distinct subpopulations of these ALDH+ cells, which made up about 0.1-0.2 percent of patients' primary tumors. In samples of metastatic melanoma -- the most aggressive form of the disease -- the percentage of ALDH+ cells was greater, even over 10 percent in some tumors, further implying the powerful danger of these cells.

"In these same ALDH+ cells, we find the markers of stem cells are upregulated and those of cell differentiation are downregulated. In addition to these clues, ALDH+ cells generate the heterogeneous cell types seen in the original tumor," says Fujita, meaning that in addition to self-renewal and tumorigenesis, ALDH+ cells fulfill the third criteria for a cancer stem cell: the ability to differentiate.

The study also shows how the ALDH gene and its protein act to create a cell's stem-like properties.

"One way ALDH makes a cancer stem cell is through the retinoic acid signaling pathway," Fujita says. The protein ALDH leads to the overproduction of retinoic acid, which in turn binds to a cell's nuclear receptors and influences the expression of many of the cell's genes -- for example, genes involved in regulating cell survival, repair, and proliferation, all of which combine to confer chemoresistance. Target cells with high ALDH and you target all the downstream effects, including the retinoic acid signaling pathway.

"Our hope is that we can intervene in this signaling, either at the level of ALDH or elsewhere in the pathway, especially to re-sensitize cells to chemotherapy. Using a new drug to take away a melanoma stem cell's chemoresistance could boost the effectiveness of existing drugs," Fujita says.


Story Source:

The above story is based on materials provided by University of Colorado Denver. The original article was written by Garth Sundem. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yuchun Luo, Katiuscia Dallaglio, Ying Chen, William A Robinson, Steven E Robinson, Martin D McCarter, Jianbin Wang, Rene Gonzalez, David C Thompson, David A Norris, Dennis R Roop, Vasilis Vasiliou, Mayumi Fujita. ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets. STEM CELLS, 2012; DOI: 10.1002/stem.1193

Cite This Page:

University of Colorado Denver. "Human melanoma stem cells identified." ScienceDaily. ScienceDaily, 23 August 2012. <www.sciencedaily.com/releases/2012/08/120823152417.htm>.
University of Colorado Denver. (2012, August 23). Human melanoma stem cells identified. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2012/08/120823152417.htm
University of Colorado Denver. "Human melanoma stem cells identified." ScienceDaily. www.sciencedaily.com/releases/2012/08/120823152417.htm (accessed October 24, 2014).

Share This



More Health & Medicine News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins