מתוך medicontext.co.il
By Karla Gale
WESTPORT, CT (Reuters Health) – Scientists may have elucidated the mechanism by which melanoma relapses follow initially successful therapy.
According to Dr. Richard E. B. Seftor of The University of Iowa in Iowa City, aggressive melanoma cells secrete a particular form of laminin that remains in the extracellular matrix. Enzymatically degraded laminin products can in turn induce less aggressive, but more hardy, melanoma cells to become more aggressive and invasive.
In the September 1st issue of Cancer Research, Dr. Seftor and colleagues describe how they investigated the genetic difference between aggressive and nonaggressive melanoma cells through the use of microarray gene chip analysis.
"We found that there are a number of genes in aggressive cells that are not turned on in less aggressive cells," Dr. Seftor told Reuters Health.
These "turned-on" genes express laminin 5 gamma-2 chain, as well as several matrix metalloproteinases, Dr. Seftor said. Enzymatic breakdown of the laminin leads the aggressive cells to form extracellular matrix patterned tubular networks. According to the research team's previous work, these networks are required for the vasculogenic mimicry exhibited by aggressive melanoma cells.
"We believe that vasculogenic mimicry might facilitate the ability of primary tumors to expand and grow at a fast rate," Dr. Seftor added.
In the next phase of their research, the investigators grew the aggressive tumor cells in a three-dimensional collagen matrix, then removed the cells. This preconditioned matrix was then capable of inducing poorly aggressive melanoma cells to form the patterned tubular networks.
Dr. Seftor postulated that, during therapy, "aggressive cells were killed, but less aggressive cells may be less responsive. As a result, you would have an increase in that population of cells."
However, he said, the aggressive cells leave behind the chemical signals, that, when encountered by the less aggressive cells, cause them to act more aggressively.
These findings may have "profound implications for the development of novel therapies directed at the extracellular matrix to alter tumor progression," the researchers conclude.
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