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

RID1B, 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 developmen
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Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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