Masters of survival in any environment, cancer cells rely on the healthy cells surrounding them for sustenance, literally leeching life from their host. They do this by rerouting blood vessels to nourish themselves, secreting chemicals to scramble immune responses, and manipulating neurons for their own benefit.  Direct growth-promoting effects of neurons in the tumor microenvironment have been described for an increasing list of cancers, with tumor innervation emerging as an important therapeutic target.  However, the nerve system’s 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 tumors exploit neuronal signals, as well as the influences of active neurons on stem cell and cancer microenvironments across a broad range of tissues.  The team states 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 for a broad range of cancers neural signaling promotes growth.   Brain cancer cells often cluster around neurons, a phenomenon called ‘perineuronal satellitosis,’ with the extent of innervation in tumors long being linked to patient outcome. Migrating cancer cells also use nerves as shortcuts into new tissues with recent studies showing the recruitment of nerves into the tumor microenvironment is necessary for stomach cancer progression.  Earlier studies from the team found glioma cells grew faster when adjacent to highly active neurons, adding to a growing body of work indicating cancer cells grow near nerves and respond to the chemical signals 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 tumor initiation and growth.

The current lit review indicates 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 tissue.  Data findings show the roles of neural elements in cancer growth are becoming increasingly clear for several malignancies. Results show cancers reciprocally modulate nervous system activity, promoting increased excitability of neurons in the brain, which in turn promotes the growth of new nerve branches in non-nervous system cancers.

The lab states understanding the influences of the nervous system on the tumor microenvironment has already highlighted new potential therapeutic avenues for cancers of the brain, prostate, pancreas, stomach, and skin.  The group notes presently underexplored are the roles neurons play in cancer growth and initiation.

The team surmises their review sheds light on the neural contributions to cancer growth and progression, elucidating novel therapeutic avenues for multiple cancers.  For the future, the researchers state 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

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