Navigation Links
Wistar scientists explain the persistence of melanoma through 'dynamic stemness'
Date:5/13/2010

Scientists at The Wistar Institute offer a new explanation for the persistent ability of melanoma cells to self-renew, one of the reasons why melanoma remains the deadliest form of skin cancer. The concept of the "dynamic stemness" of melanoma can explain why melanoma cells behave like both conventional tumor cells and cancer stem cells.

The researchers write in the May 14 issue of the journal Cell thatcontrary to other published reportsmelanoma does not appear to follow the hierarchic cancer stem cell model, where a single malignant "mother cell" both reproduces to produce new mother cells and differentiates to produce the bulk tumor population. Instead, all melanoma cells equally harbor cancer stem cell potential and are capable of inducing new tumors. Their findings reveal the unique biology of melanoma, and suggest that melanoma requires a new therapeutic approach.

"Targeting only the bulk tumor population, as most conventional anticancer therapies do, is pointless in melanoma, in that each cell can act as a seed for the tumors to rebound," said Meenhard Herlyn, D.V.M., D.Sc., professor and leader of Wistar's Molecular and Cellular Oncogenesis Program. "The other implication is that we should stop hunting for a cancer stem cell, because it won't be there."

The traditional view of cancer holds that cancers arise following a random accumulation of malignant events, e.g. mutations, gradually imparting enough growth advantages that a cell can grow unchecked. Over the last decade, scientists have developed a cancer stem cell concept that explains how the slow growth and persistence of mother cells allow tumors to persist following treatment. Melanoma, for one, seems to follow a third path, dynamic stemness, where the stem cell-like behavior is not confined to mother cells alone, Herlyn says.

In the study, Herlyn and his colleagues describe a slow-growing subpopulation of melanoma tumor cells, defined by the protein JARID1B, which is required for tumor maintenance. Genetically blocking the ability of cells to expressor producethis protein "exhausts" the tumor, preventing its proliferation. Yet unlike classic cancer stem cells, this subpopulation is highly plastic: JARID1B-expressing cells can turn off the gene, and JARID1B-non-expressing cells can turn it on.

Their findings suggest that melanoma requires a two-pronged therapeutic approach, says Herlyn. One is needed to target the bulk of the tumor, while another one should specifically target the slow-growing, JARID1B-positive subpopulation. "It's a dual therapy that we are proposing," said Herlyn.

According to the study's lead author, Alexander Roesch, M.D., of the Regensburg University Medical Center in Germany and a visiting scientist in the Herlyn laboratory at The Wistar Institute, the growth could explain the disease's notorious therapy resistance. "A slow-growing JARID1B-positive subpopulation of tumor cells, immune to most therapies, can spontaneously convert to a fast-growing JARID1B-negative population, which can rapidly replenish the tumor," Roesch said.

The present study arose when Roesch discovered a link between the potential of JARID1B to decrease proliferation of melanoma cells and control stemness. He decided to see whether JARID1B could be a marker of slow growing melanoma stem cells. Initially, the results were promising, he says. JARID1B-expressing cells were slow-growing (as stem cells often are), and rare, accounting for about 5 percent of the tumor population. "At this point we were really happy because we thought we had found a cancer stem cell marker," Roesch said.

But then, two unexpected results occurred. First, Roesch found that all melanoma cells were equally capable of initiating tumors in a mouse model, regardless of whether they expressed JARID1B or not. Second, he found that JARID1B expression did not conform to the traditional model of stem cell development cells that expressed the gene could turn it off, and cells that didn't, could turn it on. In other words, the gene's expression was plastic, rather than stable. "Basically, our data suggest that every melanoma cell can serve as source for indefinite replenishment of the tumor," said Roesch.

At the moment, the researchers do not suggest that the cancer stem cell model is wrong in any other tumors; their results apply only to melanoma, which may represent a special case.


'/>"/>

Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

Related medicine news :

1. Wistar-led research team discovers genetic pattern that indicates early-stage lung cancer
2. Mass. Eye and Ear receives NEI grant renewal for growing clinical/scientists
3. Scientists Map Neanderthal Genome
4. Genome breakthrough allows scientists to identify and profile tumor cells from very small samples
5. Scientists Unravel Secret of HIV Resistance
6. A century-old puzzle comes together: Scientists ID potential protein trigger in lung disease sarcoidosis
7. President Bill Clinton and South African Health Minister Aaron Motsoaledi to join 25,000 scientists, people living with HIV, and other stakeholders at XVIII International AIDS Conference in Vienna
8. Scientists Find Cause of Involuntary Mirror Movements
9. Scientists Discover Substance That Causes Pain
10. Scientists Find Way to Heal Broken Bones Faster
11. Scientists Report Key Finding in Breast Cancer Research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... SAN LUIS OBISPO, Calif. (PRWEB) , ... October 13, 2017 , ... ... with Alzheimer’s or dementia. However, many long-term care insurance companies have a waiver for ... mean is the 90-day elimination period, when the family pays for care, is often ...
(Date:10/13/2017)... Texas (PRWEB) , ... October 13, 2017 , ... Yisrayl ... this week that explains one of the most popular and least understood books in ... like cryptic and puzzling descriptions that have baffled scholars for centuries. Many have tossed ...
(Date:10/13/2017)... ... ... “America On The Brink”: the Christian history of the United States and the loss ... author, William Nowers. Captain Nowers and his wife, Millie, have six children, ten ... the Navy. Following his career as a naval aviator and carrier pilot, he ...
(Date:10/12/2017)... ... October 12, 2017 , ... The ... demand of today’s consumer and regulatory authorities worldwide. From Children’s to Adults 50+, ... to meet the highest standard. , These products are also: Gluten Free, ...
(Date:10/12/2017)... Rockville, Maryland (PRWEB) , ... October 12, 2017 ... ... a magnetic drug delivery system that we intend to develop to enable prevention ... regimens can lead to severe hearing loss, especially in pediatric patients. For cisplatin, ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... 2, 2017 Diplomat Pharmacy, Inc. (NYSE: ... and Consulting, LLC , and named its founder as ... in Tennessee , will operate under ... EnvoyHealth,s service offerings for health care partners to include ... "In an interoperable world, technology delivers ...
(Date:9/28/2017)... 28, 2017 Hill-Rom Holdings, Inc. (NYSE: HRC), ... call and webcast on Friday, November 3, 2017, beginning ... ending at approximately 8:30 a.m. (CDT) / 9:30 a.m. ... 2017 financial performance and guidance for 2018, Hill-Rom executives ... enhance operational performance, and long-range financial outlook through 2020. ...
(Date:9/25/2017)... , Sept. 25, 2017  EpiVax, Inc., a ... design, and immune-engineering today announced the launch of ... development of personalized therapeutic cancer vaccines. EpiVax has ... exclusive access to enabling technologies to the new ... will lead EpiVax Oncology as Chief Executive Officer. ...
Breaking Medicine Technology: