29 January 2015
New insight has been gathered into how cancer is able to turn healthy cells into bad ones. A team from Rice University, Texas, has identified an element of cell signaling that the disease uses to hijack the communication process and spread.
In their computational study, the researchers at the Center for Theoretical Biological Physics revealed how cancer cells can take advantage of the cell's communication system. The diseased cells use this mechanism to tell surrounding cells whether to be like them or not.
Published in the Proceedings of the National Academy of Sciences, the study follows on from similar research conducted last year in which researchers mapped the flow of information through genetic circuits involved in cancer metastasis.
The team, led by biophysicists Eshel Ben-Jacob and José Onuchic from Rice University, discovered how cancer is able to use a mechanism for cell-cell interaction - known as notch signaling - to promote metastasis. This is activated when a delta or jagged ligand of one cell interacts with the notch receptor on an adjacent one and are crucial for embryonic development and healing wounds.
"At the heart of our new understanding is that the primary agents of metastasis are clusters of hybrid epithelial (nonmobile) and mesenchymal (migrating) cells," Dr Ben-Jacob said. "These, and not the fully mesenchymal cells, are the 'bad actors' of cancer progression that pose the highest risk. By acting together, these hybrid cancer cells have a better chance to evade the immune system during migration and can better survive while circulating in blood vessels."
He added that this multifaceted mechanism by which notch-delta-jagged signaling promotes cancer progression has been a mystery until now, but recent experimental studies have revealed the jagged ligand plays a critical role in tumour progression.
These new findings provide a novel theoretical framework for scientists who study the behaviour of cells as it shows the presence of jagged ligands, which can give rise to sender/receiver hybrid cells that send a signal. Although this is useful for embryonic development and healing, it can also be manipulated by cancer cells.
"We realised that hybrid cancer cells can take advantage of that characteristic to establish stable interactions and turn them into 'assault teams' that migrate together during metastasis," Dr Onuchic said.
Dr Ben-Jacob said previous research in this area has focused heavily on notch-delta signaling, where one cell (the sender) expresses high-notch receptor and low-delta ligand. The other (the receiver) expresses low notch and high delta, which leads to the two cells adopting opposite fates.
"Since jagged seemed to play a similar role to delta, the focus has been on notch-delta," Dr Ben-Jacob said. "We were motivated to look closer and focus on the effect of the differences between these ligands."
The researchers suggested cells' internal expression of jagged may also increase the production and maintenance of therapy-resistant cancer stem cells. Their findings are a step closer to better understanding the signaling mechanisms cancer cells use to evade the immune system and treatment.