TRPM7 is the protein recently discovered by the researchers of Johns Hopkins University, which should have the function of preventing cancer cells from entering the bloodstream and spreading to other parts of the body.
The results of the Research have been published in the scientific journal Science Advances.
TRPM7: this is what its function is
Kaustav Bera, Ph.D. of Johns Hopkins University. candidate in chemical and biomolecular engineering and lead author of the study, which was conducted with colleagues from the University of Alberta and Universitat Pompeu Fabra, said: “We found that this protein, TRPM7, senses the pressure of the fluid flowing in the circulation and prevents cells from spreading through the vascular system “.
“We found that metastatic cancer cells have greatly reduced levels of this sensor protein, and that is why they efficiently enter the circulation rather than move away from the fluid flow “, Bera added.
This new research has shed light on a little-known part of the metastasis called intravasation, when the Cancer cells that have separated from a primary tumor enter the bloodstream to travel to other parts of the body and establish colonies. The panel also demonstrated that artificially increasing TRPM7 expression in cancer cells can help stop intravascularization and ultimately metastasis.
Other research had already shown how TRPM7 has the function of regulating calcium in cells, but according to the Hopkins researchers, this new view of its role in cell migration is promising: “The process is similar to what happens when you touch a hot kettle, feel it is hot and remove your hand “, explained the senior author of the study Konstantinos Konstantopoulos, professor of chemical and biomolecular engineering and a member of the Johns Hopkins Kimmel Cancer Center.
“In static conditions, the cells si insinuate into the microchannels, while 40-60% reverses the direction when the fluid flows.
The protein detects the flow of fluid in the circulatory system and instructs the cell to reverse the direction, thus inhibiting intravasation “Konstantopoulos continued.
Typically, cells in the human body, such as muscle cells, the fat cells and the epithelial cells, remain contained in their respective regions. The main exception is blood cells, which patrol the body fighting pathogens. Cancer cells, on the other hand, have mutations that allow them to travel and spread.
It is at this point in the spread that cancer becomes much more dangerous. “Many people will be diagnosed with primary cancer, but as long as this tumor is contained, a surgical procedure can save the person”, he has declared Christopher Yankaskas, lead author and former member of Konstantopoulos lab who is now a scientist at Thermo Fisher. Scientific.
For their initial experiment, the researchers observed fibroblast cells seals that moved through microchannels arranged perpendicularly in a ladder configuration where the fluid could be controlled. When these cells encountered channels in which fluid was moving, they reversed their direction in response to the shear stress exerted by the flow. However, when the cells encountered channels where the fluid was not moving, they entered them.
The researchers then used a process known as RNA interference to prevent cells from expressing TRPM7. What they observed was surprising: when this sensor protein was disabled, healthy cells no longer reversed direction in response to flow. “Imagine lifting the kettle with an oven mitt, which reduces your sensitivity to heat“Said Konstantopoulos.
In subsequent experiments the researchers found that normal cells had higher levels of TRPM7 than sarcoma cells (a type of cancer cell) and that artificial expression of the protein in cancer cells increased their sensitivity to fluid flow. (2)
When normal cells reverse their migration direction, they avoid exposure to shear stress, but that’s not the case with cancer cells, Konstantopoulos explained. “Cancer cells are less sensitive, which is why they continue to enter the circulatory system “.
“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 it.A separate analysis of human patient data showed that those with osteosarcoma, breast cancer, stomach and liver who expressed high levels of TRPM7 were more likely to live longer than those with lower levels of the protein.
More research will be needed, but the scholars hope the findings could lead to new cancer therapies using theactivation of CRISPR, an exciting emerging DNA modification tool.
“We will need further developments before we can bring it into the clinical setting, but we believe we are providing, for the first time, a definitive picture of the role of TRPM7 in a crucial phase of tumor metastasis“, Concluded Konstantopoulos.