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Mechanisms of cancer dissemination along nerves

Opinion | Published: 06 May 2016

Mechanisms of cancer dissemination along nerves

Nature Reviews Cancer volume16, pages399–408 (2016) | Download Citation


The local extension of cancer cells along nerves is a frequent clinical finding for various tumours. Traditionally, nerve invasion was assumed to occur via the path of least resistance; however, recent animal models and human studies have revealed that cancer cells have an innate ability to actively migrate along axons in a mechanism called neural tracking. The tendency of cancer cells to track along nerves is supported by various cell types in the perineural niche that secrete multiple growth factors and chemokines. We propose that the perineural niche should be considered part of the tumour microenvironment, describe the molecular cues that facilitate neural tracking and suggest methods for its inhibition.

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C. Cohen is thanked for her editorial assistance. N. Rada is thanked for her artistic work. Supported by the Israeli Science Foundation, Binational US–Israel Science Foundation, Israeli Cancer Research Found, Israel Cancer Association, Rappaport Institute at the Technion and the Clinical Research Institute at Rambam.

Author information


  1. Laboratory for Applied Cancer Research, Department of Otolaryngology Head and Neck Surgery, Head and Neck Center, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion-Israel Institute of Technology, Haalia Street No. 8, Haifa, Israel.
    • Moran Amit
    • , Shorook Na’ara
    •  & Ziv Gil

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ziv Gil.

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  1. 1.Supplementary informationSupplementary information S1 (table)


Desmoplastic reaction

Also known as desmoplasia, the desmoplastic reaction is the growth of fibrous tissue secondary to an insult such as a tumour or surgery.Dorsal root ganglia

(DRG). Also known as spinal ganglia, DRG are clusters of nerve cell bodies (a ganglia) in a posterior root of a spinal nerve.Endoneurial space

The anatomical space between the deepest layer of nerve covering, called the endoneurium, and the peripheral nerve fibres.Euclidean velocity

Directional vector of velocity defined not only by magnitude, but also by direction.Pancreatic afferents

These afferent nerve fibres are sensory neurons extending far from the nerve cell body in the coeliac ganglia. They conduct pain sensation by carrying nerve impulses from sensory receptors towards the central nervous system.Parasympathetic cholinergic fibres

These components of the autonomic nervous system are responsible for the body’s activities when it is at rest. They are called cholinergic after the main neurotransmitter, acetylcholine.Perineural space

The anatomical space between the most superficial nerve covering, also known as the epineurium layer, and the middle layer, called the perineurium, in peripheral nerves.Perineurium

Peripheral fibres are each wrapped in a protective sheath known as the endoneurium. These are bundled together into fascicles, each surrounded by a protective sheath known as the perineurium.Peripheral glial cell

Schwann cells are the principal peripheral glial cells that function to support neurons in the peripheral nervous system.Sensory fibres

Nerve fibres that deliver sensory information (for example, pain), from a peripheral organ to the central nervous system.Sympathetic nervous system

A component of the autonomic nervous system responsible for maintaining homeostasis and stimulating the body for flight-or-fight response. In peripheral nerves, the main postganglionic sympathetic neurotransmitter is noradrenaline, which activates α- and β-adrenergic receptors.Visceral hypersensitivity

Cancer-associated altered visceral perception caused by hyperexcitability of the neurons in the visceral afferent nervous system. Characterized by a lowered threshold for abdominal pain and discomfort.Wallerian degeneration

A process that results after a nerve injury, in which the part of the axon separated from the cell body of the neuron degenerates distal to the injury.

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06 May 2016



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