Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Explain The Persistence Of Melanoma Through “Dynamic Stemness”

14.05.2010
Findings Suggest Each Melanoma Cell Capable of “Cancer Stem Cell” Behavior

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 that—contrary to other published reports—melanoma 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 express—or produce—this 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.

Along with senior author Herlyn and first author Roesch, co-authors from the Herlyn laboratory include staff scientist Mizuho Fukunaga-Kalabis M.D., Ph.D.; post-doctoral fellows Susan E. Zabierowski, Ph.D., and Adina Vultur, Ph.D.; research technician Elizabeth C. Schmidt; research associate Patricia A. Brafford; and visting scientist Devraj Basu, M.D., Ph.D., of the University of Pennsylvania School of Medicine. Co-authors also include Phyllis Gimotty, Ph.D., of the University of Pennsylvania School of Medicine and Thomas Vogt, M.D., Regensburg University Medical Center.

The research was supported by grants from the US National Institutes of Health and the German Research Foundation.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures.

Greg Lester | Newswise Science News
Further information:
http://www.wistar.org

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

A new dead zone in the Indian Ocean could impact future marine nutrient balance

06.12.2016 | Earth Sciences

Significantly more productivity in USP lasers

06.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>