Perineural Invasion and Its Interrelationship with Neural Repair: A Review
Learning Objective: The reader will learn the intimate relationship between a tumor and its adjacent nerves that lead to perineural invasion. This process is the result of a series of molecular pathways, in part related to nerve regeneration.
Keywords: ARIA = acetylcholine receptor‐inducing activity; Akt = protein kinase B (also known as PKB); BDNF = brain-derived neurotrophic factor; BFABP = brain fatty acid binding protein, regulates the activity of an enzyme, fatty acid synthase, which has a potent influence on the regulation of the hypothalamus, potentially influencing the activity of regulation of neurones; CCL2 = stromal-derived C-C motif chemokine ligand 2; CD74 = plays an essential role in antigen presentation by mediating assembly and subcellular trafficking of the MHCII complex (major histocompatibility complex II); CNTF = ciliary neurotrophic factor; COX = cyclooxygenase, officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for formation of prostanoids including prostaglandins; CX3CL1 = a C-X3-C motif chemokine ligand 1; CX3CR1 = a fractalkine receptor or G protein-coupled receptor 13; CXCL13 = a C-X-C (a chemokine family of proteins) motif chemokine ligand 13; DHH = desert hedgehog; Egr2 = early growth response 2; ErbB =; FGF = fibroblast growth factor, a family of cell signaling proteins that are involved in a wide variety of processes, most notably as crucial elements for normal development; GAL = galanin; GALR = galanin receptor; GDNF = glial cell line-derived neurotrophic factor; GLUT-1 = glucose transporter 1; GSK3 = glycogen synthase kinase-3; IGF = insulinlike growth factor; JAM = a family of junctional adhesion molecules; Krox20 = zinc-finger transcription factor Krox20 (Krox20 is also known as Egr-1 is an early growth response gene); LIF (leukaemia inhibitory factor) = an interleukin 6 class cytokine that affects cell growth by factor-inhibiting differentiation; MAG = myelin-associated glycoprotein is a transmembrane protein of both the CNS and the peripheral nervous system; MALT1 = mucosa-associated lymphoid tissue is a protease that plays an important role in T-cell antigen receptor-induced integrin adhesion; MAPK = mitogen-associated protein kinase; MBP = mannan binding protein; MCP-1 = monocyte chemotactic protein 1; MMP = metalloproteinase; N-cadherin = is involved in cell-cell adhesion, differentiation, embryogenesis, invasion, and signaling; NCAM = neural cell adhesion molecule; NDF = neu-differentiation factor regulates Schwann cell lineage; NFATC2 = a nuclear factor of activated T-cells; NFATC4 = nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent-4; NGF = nerve growth factor; NRG1 (type I and III) = neuregulin I is a cell adhesion molecule that, in humans, is expressed in excitatory and inhibitory neurons; NRTN = neurturin a protein of the GDNF family; NT = neurotrophin (3, 4/5); Oct6 = a transcription factor controlling myelination, and it is a marker for active nerve regeneration; P0 = peripheral nerve stimulating proteins are the dominant protein in peripheral nervous system myelin; PGE2 = prostaglandin E2 = a potent inflammatory mediator; PI3 = phosphoinositide 3; PNI = perineural invasion; PNS = perineural spread; Sox10 = SRY (sex related region)-related HMGbox (homeobox)-10; TNFα = tumor necrosis factor α; TRAF = tumor necrosis factor receptor-associated factor; TrkA = tropomyosin receptor kinase A; VEGF = vascular endothelial growth factor; ZO-1 = zonula occludens-1, a peripheral membrane protein and part of a family of ZO proteins (ie, ZO-2); artemin = a neurotrophic factor in the glial cell line‐derived neurotrophic factor family of ligands; cAMP = adenylate cyclase‐cAMP (cyclic adenosine monophosphate) protein kinase is an important mediator in determining the response of a cell to external stimuli; calpain = calpain is an intracellular Ca2+-dependent (calcium dependent) cysteine protease; claudins = function as major constituents of the tight junction complexes that regulate the permeability of epithelia; collagen IV = a type of collagen found primarily in the basal lamina; connexin = connexins or gap junction proteins are structurally related transmembrane proteins that assemble to form vertebrate gap junctions; erythropoietin (retrovirus-associated DNA sequences) = a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow; fractalkine = a transmembrane chemokine that releases an extracellular soluble fragment of CXC3L1; heregulin = stimulates axon-induced mitogenesis; interleukins (IL) = a class of glycoproteins produced by leukocytes for regulating immune responses; laminins = glycoprotein components of connective tissue basement membranes that promote cell adhesion; mRNA = messenger RNA is a large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression; occludin = a protein that, in humans, is an integral plasma-membrane protein located at the tight junctions; p44/42 MAPK pathway = mitigen-associated (activated) protein kinase signaling pathway; p75NTR = neurotrophin receptor p75 affects the binding affinity and specificity of Trk (tropomyosin receptor kinase) receptor activation by neurotrophins; pleiotrophin = secreted growth factor that induces neurite outgrowth and that is mitogenic for fibroblasts, epithelial, and endothelial cells
Document Type: Research Article
Publication date: October 1, 2019
Neurographics is the peer-reviewed, bimonthly educational journal of the American Society of Neuroradiology. The journal comprises articles selected from material presented at the ASNR Annual Meeting. Neurographics also publishes other high-quality submissions that are primarily educational and have a high emphasis on a pictorial approach. Neurographics offers CME credit for reading review articles and completing quiz-based self-assessment activities.
Visit the ASNR Education Connection to view all available CME courses.
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