The metastasis they can develop in the body even years after apparently successful cancer treatment. They originate from cancer cells that have migrated from the original tumor to other organs, and that can remain inactive there for a considerable time.
The cancer cells they can migrate from the tumor to other tissues in the body, where they survive after treatment in a kind of hibernation called latency. At present, cancer medicine relies on the follow-up of cancer patients after their initial treatment to detect the awakening of these cells to form metastases.
Now a group of researchers has identified a specialized protein that appears to help prevent tumor cells from entering the bloodstream and spread to other parts of the body.
“We have discovered that this protein, TRPM7, detects the pressure of the fluid that flows in the circulation and prevents the cells from spreading through the vascular system,” they explained, detailing that they have found that metastatic tumor cells have significantly reduced levels of this sensing protein, and that is why they efficiently enter the circulation rather than away from the fluid flow.
These new findings have helped shed light on a poorly understood part of metastasis called intravasation, when cancer cells that have separated from a primary tumor enter the circulation to travel to other parts of the body and establish colonies.
According to research, the protein prevents tumor cells from spreading through blood vessels
The researchers further show that artificially increasing TRPM7 expression in tumor cells can help stop intravasation and ultimately metastasis.
“The process is similar to what happens when you touch a hot water kettle, feel that it is hot, and remove your hand. The protein detects the flow of fluid in the circulatory system and instructs the cell to reverse direction, thereby inhibiting intravasation “, they have pointed out.
For their initial experiment, the researchers observed healthy fibroblast cells moving through microchannels arranged perpendicularly in a ladder-like configuration in which fluid could be controlled. When these cells found channels where the liquid was moving, they reversed their direction in response to the shear stress exerted by the flow. However, when the cells found channels where the fluid was not moving, they proceeded to them.
The researchers then used a process known as RNA interference to block the cells from expressing TRPM7 and observed that when this sensor protein was disabled, the healthy cells no longer reversed direction in response to the flow.
NORMAL CELLS HAVE HIGHER TRPM7 LEVELS THAN SARCOMA CELLS
In subsequent experiments, the researchers found that normal cells had higher levels of TRPM7 than sarcoma cells (a type of cancer tumor cells), and that artificially expressing the protein in tumor cells increased their sensitivity to fluid flow.
When normal cells reverse their direction of migration, they avoid exposure to shear stress, but this is not the case with tumor cells, as they are less sensitive, and thus continue to enter the circulatory system. “The goal was to see if we could take these cancer cells and make them behave like normal cells and we succeeded,” they have celebrated.
A separate analysis of human patient data showed that those with osteosarcoma, breast, gastric, and liver cancer who expressed high levels of TRPM7 were more likely to live longer than those with lower levels of the protein.
The team hopes these findings can lead to New Cancer Therapies Using CRISPR Activation, an emerging DNA editing tool.
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