As they move through the body, highly aggressive tumor cells modify their environment, leaving behind a trail of chemical cues that can cause less aggressive cells moving into the area to become more aggressive. So say researchers writing in the September 1 issue of the journal Cancer Research. The new findings could have important implications for treatment of melanoma and other aggressive cancers.
Mary J.C. Hendrix of the University of Iowa and her colleagues set out to investigate the interactions between aggressive cancer cells and their extracellular matrix by focusing on certain proteins called matrix metalloproteinases (MMPs) and a molecule known as laminin 5, gamma 2 chain. Generally speaking, whereas laminins build up the matrix, MMPs break it downactivities that, among other things, affect how cancer spreads through the body. The team found that the laminin in question is produced only by aggressive melanoma cells. Likewise, the aggressive cells exhibited higher levels of two of the MMPs.
As it turns out, the interactions between the MMPs and the laminin produced by the aggressive cells cause the laminin to break into pieces that are laid down in discrete tracks in the extracellular matrix. Intriguingly, the researchers found that when they grew aggressive melanoma cells on the matrix for a short time and then replaced them with less aggressive melanoma cells, the newcomers became more aggressive, forming the vascular networks that would enable them to travel to distant parts of the body. The laminin bits deposited by the aggressive cells, the scientists determined, were instructing the meeker cells to change their ways.
"These findings show the importance of specific interactions of particular molecules in the matrix to support and perpetuate invasion and migration of tumor cells long after the original aggressive tumor cells have passed through the matrix," Hendrix remarks. "The implications of this study suggest that the matrix of tumors might serve as an excellent target to inhibit tumor cell signals, which control invasion and metastasis."