Cancer becomes far more dangerous when it spreads through the body. Now, researchers at Johns Hopkins University have identified a protein that stops cells getting into the bloodstream – and found that metastasizing cancer cells ignore it. This may reveal a new drug target for cancer treatment.
Cancer is frustratingly proactive. After it establishes itself in one part of the body, it tends to start shedding rogue cells that venture out into the bloodstream, then to other organs to set up a new “colony.” This process of metastasis makes cancer much harder to track down and remove, and as such exponentially more deadly.
In response, finding ways to prevent metastasis is a major arm of cancer research. In recent years, scientists have discovered molecules, proteins and protein signaling pathways that help tumors spread, providing a good starting point for developing drugs that target these. An existing drug has already been found to patch up leaky blood vessels that cancer cells can penetrate more easily. Coating immune cells in nanoparticles could help them hunt down rogue cancer cells in the bloodstream. Or dietary changes could reduce the chances of metastasis.
For the new study, the researchers identified a protein that may be a new potential drug target for preventing metastasis. It’s long been known to regulate calcium levels in cells, but the team has now discovered that the protein has another function that may play a role in metastasis.
"We have discovered that this protein, TRPM7, senses the pressure of fluid flowing in the circulation and stops the cells from spreading through the vascular system," says Kaustav Bera, lead author of the study. "We found that metastatic tumor cells have markedly reduced levels of this sensor protein, and that is why they efficiently enter into the circulation rather than turning away from fluid flow.”
Intriguingly, healthy cells were found to have far higher levels of TRPM7 than tumor cells, which goes a long way towards explaining why cancer can spread more readily.
The team tested the discovery with cells moving through a model bloodstream of microchannels arranged like a ladder, with the flow carefully controlled. They found that healthy fibroblast cells would reverse direction in response to fluid flow, but moved into channels where the fluid was still.
Next, the researchers blocked the cells from expressing the TRPM7 protein – and sure enough, this time they ignored the fluid flow and went right on into those fast-moving channels. Conversely, when they edited tumor cells to express the protein in higher amounts, they became sensitive to fluid flow once again.
While it’s still early days, the find could pave the way for a new type of treatment that prevents cancer metastasis by targeting the TRPM7 protein.
"We'll need further developments before we can take this to the clinical setting, but we believe we provide, for the first time, a definitive picture of the role of TRPM7 in a crucial step of tumor metastasis," says Konstantinos Konstantopoulos, senior author of the study.
The research was published in the journal Science Advances.
Source: Johns Hopkins University via Eurekalert
