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The brain: a key participant in the development of cancer?

Using NMR spectroscopy to detect cell morphology alterations in vivo

A team from IRCM (CEA/Inserm) has shown that neurons can develop within the tumoral microenvironment and furthermore contribute to the development of certain types of cancer, particularly prostate cancer. Their surprising discovery opens an entirely new field of research on the role of the nervous system and the interactions between it and the vascular and immune systems in tumorigenesis. The study was recently published in the scientific journal Nature.

Published on 17 May 2019
The production of new neurons (neurogenesis) in adults is relatively rare, occurring only in two specific structures of the brain, the dentate gyrus (in the hippocampus) and the subventricular zone. The Inserm team Atip-Avenir1, headed by Claire Magnon at IRCM2, a part of the CEA's François Jacob Institute of Biology, recently discovered that neurogenesis can also occur outside of the central nervous system, more precisely within tumors.

In 2013, that team had already shown that the infiltration of nerve fibers (originating from preexisting axons) was associated with the development and progression of prostate cancer3. Since that work, other studies have confirmed the unexpected but apparently important role of nerve fibers in the tumor microenvironment of numerous solid cancers.

In their recent work, the Atip-Avenir team went even further, demonstrating the presence of neural progenitors in the tumors of 52 patients with prostate cancer. Those progenitors were positive for a protein called doublecortin (DCX), the expression of which is normally associated with embryonic development and adult neurogenesis.  The neural progenitors appear to infiltrate the tumor, where they mature into neurons. Their presence in the tumor, according to the authors, favors the exacerbation of disease and the proliferation of metastases.

"Our surprising discovery attests to the presence of DCX+ neural progenitors outside of the adult brain," comments Claire Magnon. "Furthermore, our study showed that they participate in the formation of new neurons in the tumors."

The team also performed a range of experiments in a transgenic mouse model and found that the DCX+ neural progenitors migrated from the subventricular zone through the circulatory system to attain and reside within the tumor and metastatic nodules. Thus, there would appear to be communication between the brain and the tumor, enabling the delivery of neural progenitors from the former to the latter via the circulatory system.
The study may open new vistas for therapeutic options. For example, future treatments may target the neural progenitors while they are circulating in the blood. Complementarily, the study of neural networks within tumors may shed light on how some of them manage to resist treatments.

These results have also been shared through a press release.

1. Cancer and Microenvironment Laboratory, Atip-Avenir Team, UMR967 Inserm/IBFJ-iRCM-CEA/Paris-Sud University/Paris Diderot University, Fontenay-aux-Roses

2. Research Institute of Cellular and Molecular Radiobiology

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