A good news to prevent tumor metastasis: inhibit the spread of blood vessels

Researchers have discovered a special protein that seems to help prevent tumor cells from entering the bloodstream and spreading to other parts of the body

"We found that this protein called TRPM7 can sense the pressure of fluid flowing in the circulation and prevent cells from spreading in the vascular system," said Kaustav, PhD in Chemistry and Biomolecular Engineering at Johns Hopkins University and lead author of the study.

Bera said: "We found that metastatic tumor cells significantly reduced the level of this sensor protein, which is why they effectively enter the circulation instead of leaving the fluid flow

This discovery, published in the journal Science Advances, helps to clarify a little-known metastasis phenomenon, that is, cancer cells isolated from the primary tumor enter the blood circulation and then metastasize to the body.

The researchers further showed that artificially increasing the expression of TRPM7 in tumor cells may help prevent the intravascular metastasis of tumor cells

Researchers say that TRPM7 has long been thought to regulate calcium in cells, but this new insight into its role in cell migration is exciting

He said that this protein can sense the flow of fluid in the circulatory system and instruct cells to reverse the direction, thereby inhibiting the flow in blood vessels

Normally, cells in the human body—such as muscle cells, fat cells, and epithelial cells—are kept in their respective areas

It is in this spreading process that cancer becomes more dangerous

In their initial experiments, the researchers observed healthy fibroblasts moving in vertically arranged ladder-shaped microchannels, in which liquid can be controlled

The researchers then used a process called RNA interference to prevent cells from expressing TRPM7

In subsequent experiments, the researchers found that normal cells have higher levels of TRPM7 than sarcoma cells (a type of cancer cell), and that artificial expression of this protein in tumor cells increases their sensitivity to fluid flow

Konstantopoulos explains: “When normal cells reverse their migration direction, they avoid shear stress, but tumor cells are not

Bera said: "Our goal is to see if we can take these cancer cells out and make them behave like normal cells

Another analysis of human patient data showed that those with high levels of TRPM7 in patients with osteosarcoma, breast cancer, gastric cancer, and liver cancer were more likely to live longer than those with low protein levels

We need more research, but the research team hopes that this discovery will eventually lead to the use of CRISPR activation, an exciting emerging DNA editing tool, for new cancer treatments

Konstantopoulos said: "Before applying it to the clinic, we need further research, but we believe that for the first time, we provide a clear picture of the role of TRPM7 in the key steps of tumor metastasis
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The fluid shear stress sensor TRPM7 regulates tumor cell intravasation