Brain tumor cells exploit a mechanism normally used by healthy brain cells to promote their own multiplication.
Gliomas include several cancers that develop from cells of the nervous system. Some of their cells strongly resemble oligodendrocyte precursor cells. In healthy people, these immature cells can later become cells that help insulate nerve fibers.
Researchers already knew that neuronal activity could promote the growth of certain gliomas. A molecule called neuroligin-3, or NLGN3, is released into their surroundings when nerve cells are active. What remained unclear was precisely how tumor cells detected this signal.
The new study identifies a chain of events. NLGN3 first binds to a protein present on the cell surface. This interaction changes the tension of their membrane, the very thin envelope that separates the inside of the cell from its surroundings.
This change then activates PIEZO1. This protein forms a channel sensitive to the mechanical forces exerted on the membrane. When it opens, it therefore transforms a physical change in the membrane into a signal the cell can use. The experiments show that PIEZO1 plays a major role in the response to NLGN3.
The researchers deactivated PIEZO1 in glioma cells through genetic modification. The response triggered by NLGN3 then decreased sharply. In mice bearing tumors derived from human cells, the absence of PIEZO1 also reduced the multiplication of cancer cells after four weeks.
The mechanism is not limited to cancer. In healthy oligodendrocyte precursor cells, the same signaling chain appears to help keep the cells in their immature state. The glioma would therefore hijack a normal brain function for its own growth.
This distinction is important when considering future treatments. Blindly blocking this mechanism could also disrupt healthy cells. Nevertheless, the study identifies several stages that could be investigated as potential targets.
These results still come largely from cultured cells and animal models. Future research will need to determine which steps can be slowed in a tumor without disrupting the normal functioning of brain cells.