TRPM7 Protein Found To Play Key Role in Metastasis Regulation

Researchers from John Hopkins University have identified a specialized protein that appears to help prevent tumor cells from entering the bloodstream and spreading to other parts of the body. Their study was published in Science Advances. 

"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," said lead author Kaustav Bera. "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.”

For their initial experiment, the researchers observed healthy fibroblast cells moving through microchannels arranged perpendicularly in a ladder-like configuration in which the fluid could be controlled. When these cells encountered channels where fluid was moving, they reversed their direction in response to the shear stress exerted from the flow. However, when the cells encountered channels where fluid wasn't moving, they proceeded into them.

The researchers then used RNA interference to block the cells from expressing TRPM7. When this sensor protein was disabled, the healthy cells no longer reversed direction in response to the flow. "Imagine you then pick up the kettle with an oven mitt, which reduces your sensitivity to the heat," said researcher Konstantinos Konstantopoulos. In subsequent experiments, the researchers found that normal cells had higher levels of TRPM7 than sarcoma cells (a type of cancerous tumor cells) and that artificially expressing the protein in the tumor cells increased their sensitivity to the fluid flow.

"The goal was to see if we could take these cancerous cells and make them behave like normal cells," said Bera. "And we managed to do that."