Researchers have found that a signal molecule produced by Schwann cells found in benign neuroblastomas acts as a natural ‘brake’ keeping them benign and preventing their uncontrolled growth. This also works on malignant neuroblastoma cultures.
While energising a tumour with a growth factor to halt it does not sound logical, with neuroblastomas the Schwann cells trigger the maturation of nerve cells and bring the growth to a halt.
Schwann cells produce a signalling molecule called epidermal growth factor like 8 (EGFL8). The researchers showed that EGFL8 stimulates the differentiation, or maturation, of neuroblastoma cells. “Until recently, we only knew that this protein existed, but its function was not known. We now for the first time know where EGFL8 is produced and how it acts,” explained study author Sabine Taschner-Mandl, PhD, head of the Tumor Biology Group at St. Anna Children’s Cancer Research Institute. The study results also showed that high levels of EGFL8 were linked to improved survival rates in neuroblastoma patients.
“In cell cultures, we have demonstrated that Schwann cells as well as their secreted signaling molecules exert anti-tumour effects, even in aggressive neuroblastoma cells. Thus, we are able to exploit a process that occurs naturally in benign neuroblastomas to stop the malignant ones,” Sabine Taschner-Mandl and her colleague Tamara Weiss, PhD, from the Medical University of Vienna, explained.
However, there is still much to be discovered about how the interplay of Schwann cells with the rest of the body; currently the researchers are examining how they interact with immune cells.
The study also uncovered a significant finding: that Schwann cells in benign neuroblastomas have a similar cellular status to those that support healing in injured peripheral nerves. Schwann cells in the tumour were found to express repair-associated genes and demonstrated repair functions. “It is amazing that we have discovered a signalling molecule that plays a role in both tumour development of benign neuroblastomas and regeneration of injured nerves. Since EGFL8 stimulates the formation of nerve cell extensions, it could be of great importance for the treatment of injured nerve fibers”, said Tamara Weiss.
Source: Medical Xpress
Journal information: Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor like protein 8, Nature Communications (2021). DOI: 10.1038/s41467-021-21859-0
