Nerve Growth Factor and Artemin Are Paracrine Mediators of Pancreatic Neuropathy in Pancreatic Adenocarcinoma

  title={Nerve Growth Factor and Artemin Are Paracrine Mediators of Pancreatic Neuropathy in Pancreatic Adenocarcinoma},
  author={G{\"u}ralp O Ceyhan and Karl‐Herbert Sch{\"a}fer and Annika G Kerscher and Ulrich Rauch and Ihsan Ekin Demir and Mustafa Kadihasanoglu and Carolin B{\"o}hm and Michael W. M{\"u}ller and Markus W. B{\"u}chler and Nathalia A. Giese and Mert Erkan and Helmut Friess},
  journal={Annals of Surgery},
Objective:To further characterize the neurotrophic attributes of pancreatic cancer (PCa). Summary Background Data:PCa is characterized by neuropathic alterations which are resulting in pancreatic pain. To further characterize pancreatic neuropathy, we aimed: to analyze whether neuropathic alterations in PCa are only limited to the tumor-core or whether they are similarly encountered in neural structures in the noncancerous pancreas, to demonstrate whether PCa features neurotrophic attributes… 
The neurotrophic factor neurturin contributes toward an aggressive cancer cell phenotype, neuropathic pain and neuronal plasticity in pancreatic cancer.
It is shown that PCC produce the neurotrophic factor NRTN, which reinforces their biological properties, triggers neuroplastic alterations, NI and influences pain sensation via the GFRα-2 receptor in PCa.
Neuroplastic changes in a mouse model of pancreatic ductal adenocarcinoma
It is found that although disease time course varied, pancreatic cancer typically developed by 16 weeks of age, however pancreatic neurotrophic factor mRNA expression was up-regulated and pancreatic innervation increased dramatically prior to this time point, which demonstrates that the nervous system participates in all stages of PDAC, including those that precede appearance of cancer.
Systemic Depletion of Nerve Growth Factor Inhibits Disease Progression in a Genetically Engineered Model of Pancreatic Ductal Adenocarcinoma
Anti-NGF treatment beginning at 4 weeks may increase inflammation and negatively impact disease, however, treatment starting at 8 weeks (after disease onset), reduces neural inflammation, neural invasion, and metastasis.
Perineural Mast Cells Are Specifically Enriched in Pancreatic Neuritis and Neuropathic Pain in Pancreatic Cancer and Chronic Pancreatitis
The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas.
Neuronal plasticity in chronic pancreatitis is mediated via the neurturin/GFRα2 axis.
The NRTN/GFRα2 axis is activated during the course of CP and represents a major key player in the reactive neural alterations in CP, the first study to provide functional evidence for the contribution of neurotrophic factors to neuroplasticity in CP.
Neural plasticity in pancreatitis and pancreatic cancer
Novel possibilities for mechanistically uncovering the role of the nervous system in pancreatic disease progression are discussed, as demonstrated by tissue and neural damage inducing neuropathic pain, and activated neurons releasing mediators that modulate inflammation and cancer growth.
Title: Neuroplastic changes occur early in the development of pancreatic ductal adenocarcinoma
The results demonstrate that the nervous system participates in all stages of PDAC, including those that precede appearance of cancer, which has been shown to be a precipitating event that can accelerate the transition of precancerous lesions to cancer.
Nerves and Pancreatic Cancer: New Insights into A Dangerous Relationship
The main molecules and signaling pathways implicated in PNI are discussed and their roles in the PDAC are discussed.
Neuroplastic changes occur early in the development of pancreatic ductal adenocarcinoma.
The results demonstrate that the nervous system participates in all stages of PDAC, including those that precede the appearance of cancer.
Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling
It is reported that the intratumoral microenvironment is a mediator of PDA-associated neural remodeling (PANR), and factors such as ‘SLIT2’ (an axon guidance molecule), which is expressed by cancer-associated fibroblasts (CAFs), that impact on neuroplastic changes in human PDA.


Pancreatic Neuropathy Results in “Neural Remodeling” and Altered Pancreatic Innervation in Chronic Pancreatitis and Pancreatic Cancer
This novel phenomenon of “neural remodeling” shows how pancreatic neuropathic pain and “visceral neuropathy” are associated with altered pancreatic innervation in CP and PCa.
The Neurotrophic Factor Artemin Promotes Pancreatic Cancer Invasion
Artemin expression was not associated with pain in PDAC, however by increasing cancer cell invasion, Artemin seems to influence neural invasion and thereby contribute to cancer cell spreading along pancreatic nerves.
Pancreatic neuropathy and neuropathic pain--a comprehensive pathomorphological study of 546 cases.
Investigate whether neuropathic changes like pancreatic neuritis, increased neural density, and hypertrophy are phenomena only in CP or whether they are also evident in other pancreatic disorders as well, and study possible variations in neural cancer cell invasion among malignant pancreatic tumors.
The neurotrophic factor artemin influences the extent of neural damage and growth in chronic pancreatitis
Overexpression of artemin in chronic pancreatitis might function as a compensatory upregulation in order to repair neural damage incurred by ongoing pancreatic inflammation.
Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer.
  • Z. Zhu, H. Friess, M. Büchler
  • Biology, Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 1999
Enhanced expression of the NGF/TrkA system may influence perineural invasion and may contribute to the pain syndrome in human pancreatic cancer.
Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma: Expression patterns and effects on In vitro invasive behavior
The data suggest the possibility that paracrine and/or autocrine NT‐Trk interactions may influence the phenotype (possibly the invasive behavior) of PDAC.
Interaction of pancreatic ductal carcinoma with nerves leads to nerve damage.
Neurotrophin-Trk receptor interactions in neoplasia: a possible role in interstitial and perineural invasion in ductal pancreatic cancer.
This work has focused on studies of neurotrophin-Trk/p75(NGFR) expression and interactions in pancreatic ductal carcinoma (PDAC) and their potential role in the perineural invasive phenotype characteristic of this cancer.
Vanilloids in pancreatic cancer: potential for chemotherapy and pain management
Resiniferatoxin induced apoptosis in pancreatic cancer cells indicates that vanilloids may be useful in the treatment of human pancreaticcancer, and vanilloid might be a novel and effective treatment option for neurogenic pain in patients with Pancreatic cancer.
Nerve growth factor sensitivity is broadly distributed among myenteric neurons of the rat colon
It is concluded that functional receptors for NGF are widely distributed among the diverse enteric phenotypes and argue for a novel NGF‐mediated regulatory system within the ENS.