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    It is known that cancer cells rely on the healthy cells which surround them for sustenance. Tumours reroute blood vessels to nourish themselves, secrete chemicals that scramble immune responses, and recruit then manipulate neurons for their own gain.  Direct growth-promoting effects of neurons in the tumour microenvironment have been described for an increasing list of cancers, with tumour innervation emerging as an important therapeutic target.  However, the neurons’ role has only been investigated in a handful of cancers, with the full molecular details of cancer-nerve partnerships still being worked out.  Now, a literature review from researchers at Stanford University investigates how tumours exploit neuronal signals, and what is known about the influences of active neurons on stem cell and cancer microenvironments across a broad range of tissues.  The team state that their review gives an up-to-date picture of the neural regulation of cancer.  The opensource study is published in the journal Trends in Cancer.

    Previous studies show that for a broad range of cancers neural signaling promotes growth.   Brain cancer cells often cluster around neurons, a phenomenon called ‘perineuronal satellitosis,’ and the extent of innervation in tumours has long been linked to patient outcome. Migrating cancer cells also use nerves as shortcuts into new tissues with recent studies showing that recruitment of nerves into the tumour microenvironment is necessary and sufficient for stomach cancer progression, and that blocking a neurotransmitter in the nerves that line the stomach could represent a novel therapy.  Earlier studies from the team found that glioma cells grew faster when adjacent to highly active neurons.  The paper is part of a growing body of work indicating that cancer cells grow near nerves and respond to the chemical signals that neurons secrete.  The current lit review investigates the functions of neuronal activity in tissue development, homeostasis, and plasticity, together with the emerging roles for active neurons in tumour initiation and growth.

    The current lit review shows that nervous system activity strongly modulates the function of stem and precursor cells, thereby influencing organ development, maintenance, plasticity, and regeneration in a diverse range of tissues; these neuron-mediated developmental mechanisms are hijacked in malignancy.  Data findings show that the roles of neural elements in cancer growth are becoming increasingly clear for several malignancies. Results show that cancers reciprocally modulate nervous system activity, promoting increased excitability of neurons in the brain, which in turn promotes growth of new nerve branches in non-nervous system cancers.

    The lab state that understanding the influences of the nervous system on the tumour microenvironment has already highlighted new potential therapeutic avenues for particular cancers of the brain, prostate, pancreas, stomach, and skin. They go on to add that targeting neuron–cancer cell interactions may prove a powerful therapeutic strategy.  The group note that presently underexplored are the roles neurons play in cancer growth and initiation, and the use of modern neuroscience techniques for modulating neuronal activity, such as optogenetics or chemogenetics, in the context of cancer models.

    The team surmise that their review sheds light on the neural contributions to cancer growth and progression, elucidating novel therapeutic avenues for cancers of the brain, prostate, stomach, pancreas, and skin.  For the future, the researchers state that as cancer treatments often target tumours by cutting off blood vessels and other nutrient supply routes, it will be interesting to learn whether it may be possible to target cancer via nerves using analogous therapies or by simply blocking secreted neural growth factors.

    Source: Stanford Medicine

    The image shows perineuronal satellitosis in the pons of a young child with pontine glioma (DIPG). The fluorescent image shows neurons (green) in co-culture with pediatric glioma cells (blue). Credit: Venkatesh and Monje.

    The image shows perineuronal satellitosis in the pons of a young child with pontine glioma (DIPG). The fluorescent image shows neurons (green) in co-culture with pediatric glioma cells (blue). Credit: Venkatesh and Monje.


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