A team of researchers from the German Cancer Research Center uncovered an activated form of a signaling molecule in blood vessels that can reprogram itself to spread cancer.
Researchers have known endothelial cells, which line the inner wall of blood vessels, play an important role in the growth and spread of cancer.
The study, conducted by researchers at the German Cancer Research Center and the Medical Faculty Mannheim of Heidelberg University, may have uncovered the way endothelial cells promote growth in cancer cells.
Researchers found high levels of the activated form of a signaling molecule called Notch when they examined blood vessel lining from lung, breast and bowel tumors, finding much higher levels of the molecule in tumor cells than in cells from healthy organs.
Notch works to regulate the development of organs in embryos and is the signaling protein in adults that regulates the activity of blood stem cells. The study suggests higher levels of Notch activation in the tumor endothelium encourage cancer to spread, resulting in a poorer prognosis for patients.
Although it was known that aberrant Notch signaling could turn cells cancerous, the new study discovered that the tumor cells themselves are responsible for Notch activation when in contact with endothelial cells.
Researchers found that the more activated Notch is in the tumor endothelium, the more cancer can spread into the bloodstream and lungs.
“Taken together, the results show a very clear picture,” Andreas Fischer, a medical researcher from the Helmholtz University Junior Research Group, said in a press release. “The tumor cells promote their spread in the body in multiple ways by activating Notch and thus reprogramming endothelial cells for their own purposes. We therefore wanted to find out if we could interrupt this disastrous mechanism.”
Fischer and his team were able to block Notch in mice with an antibody in the contact molecule VCAM1, which resulted in less cancer spread to the lungs and dampened the amount of immune cells invading the tumor to promote growth.
“Notch is a universal signaling molecule and this makes it difficult to exert therapeutic influence on it without interfering with vital processes,” Fischer said. “But a targeted short-term use of blocking antibodies might be a promising approach for suppressing the dangerous spread of tumors.”
The study was published in Cancer Cell.
March 3, 2017