Researchers found that it is possible to help stop intravasation in cancer cells, and ultimately stop metastasis, by artificially encouraging the expression of a particular protein.
A breakthrough study led by members from the Johns Hopkins University in Baltimore also sheds light on the mechanics behind intravasation, or the part of cancer cell movement where it infected cells separate from the primary tumor, crosses vessel walls, and enters the bloodstream or the lymph network. This allows them to travel and spread to other parts of the body and establish tumor colonies.
Details of their new discovery are presented in the latest Science Advances, in a report titled "The fluid shear stress sensor TRPM7 regulates tumor cell intravasation."
Shear Stress Protein That Could Halt Cancer Cell Spread
The protein that could potentially halt tumor cell intravasation and metastasis is called TRPM7, which is a protein that can sense the pressure of fluid moving along a circulation and signals cells from moving any further in a vascular system.
"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," explains Kaustav Bera, lead author of the study and a Ph.D. candidate in chemical and biomolecular engineering from Johns Hopkins University, in a press release from the university.
In their study, researchers were able to successfully demonstrate that by artificially increasing the TRPM7 expression in tumor cells, intravasation is prevented and as a consequence, metastasis is prevented.
A New Purpose for a Previously-Known Receptor
As reported in a 2018 study in the journal Cellular and Molecular Life Sciences, the protein TRPM7 has been previously identified and is known to regulate calcium concentration in cells. However, the new study promises a new potential for the protein. Senior study author Konstantinos Konstantopoulos, chemical and biomolecular engineering professor and part of the Johns Hopkins Kimmel Cancer Center, likened the process to touching a hot object, sensing and identifying that it's hot, and instinctively removing the hand.
In their study with the TRPM7, researchers observed how the protein senses the flow of fluids in the circulatory systems and its ability to instruct the cell to reverse its direction, and with it, preventing intravasation.
They also explained that under normal conditions, human cells such as those found in the muscles, fats, organs, and the skin, usually stay where they are. The main exception is blood cells that move around the body to transport materials and defend the body against foreign materials. However, there are also cancer cells that have mutations allowing them to travel and spread to different parts of the body.
In their initial experiments, researchers first observed samples of healthy fibroblast cells moving through microchannels arranged in a configuration where the fluid remains controllable. When the cells passed through channels with moving fluids, they began moving in the opposite direction - a response driven by the shear stress exerted by the flowing fluid on the cells. On the other hand, when the cells entered channels with no moving fluid, they continued moving.
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