Neurotrophins and their involvement in digestive cancers

Blondy, Sabrina; Christou, Niki; David, Valentin; Verdier, Mireille; Jauberteau, Marie‐Odile; Mathonnet, Muriel; Perraud, Aurélie

doi:10.1038/s41419-019-1385-8

Cited by 51 publications

(55 citation statements)

References 78 publications

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“…Their expression thus leads to neuroattraction and, at the same time, could induce activation of neurotrophin signaling within cancer cells themselves. Neurotrophins and their receptors are attracting increasing attention as therapeutic targets in many cancer types, as pharmacological interventions against this signaling axis have the potential to not only target cancer cells directly, but also to inhibit neurogenesis and its stimulatory effects on cancer progression and pain [73,84]. Indeed neural regulation represents an emerging targetable pathway for the treatment of cancer [75,76,78,85].…”

Section: Discussionmentioning

confidence: 99%

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Pagella

Catón

Meisel

et al. 2020

Cells

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Ameloblastomas are locally invasive and aggressive odontogenic tumors treated via surgical resection, which results in facial deformity and significant morbidity. Few studies have addressed the cellular and molecular events of ameloblastoma onset and progression, thus hampering the development of non-invasive therapeutic approaches. Tumorigenesis is driven by a plethora of factors, among which innervation has been long neglected. Recent findings have shown that innervation directly promotes tumor progression. On this basis, we investigated the molecular characteristics and neurotrophic properties of human ameloblastomas. Our results showed that ameloblastomas express dental epithelial stem cell markers, as well as components of the Notch signaling pathway, indicating persistence of stemness. We demonstrated that ameloblastomas express classical stem cell markers, exhibit stem cell potential, and form spheres. These tumors express also molecules of the Notch signaling pathway, fundamental for stem cells and their fate. Additionally, we showed that ameloblastomas express the neurotrophic factors NGF and BDNF, as well as their receptors TRKA, TRKB, and P75/NGFR, which are responsible for their innervation by trigeminal axons in vivo. In vitro studies using microfluidic devices showed that ameloblastoma cells attract and form connections with these nerves. Innervation of ameloblastomas might play a key role in the onset of this malignancy and might represent a promising target for non-invasive pharmacological interventions.

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Section: Discussionmentioning

confidence: 99%

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Pagella

Catón

Meisel

et al. 2020

Cells

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“…Neurotrophins is a family of proteins that regulates the differentiation and survival of nerve cells. It is activated by engaging special receptors, such as Trk tyrosine kinase receptors and p75 neurotrophin receptor [33]. The neurotrophin signaling pathway is regulated by connecting multiple intracellular signaling cascades [34].…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of tears and serum for dry eye disease using ovariectomized cynomolgus monkey

Yang

Wang

et al. 2020

Preprint

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Background Ovariectomized cynomolgus monkey 30 months after surgery was selected as the research object to identify protein changes in tears and serum to provide a reference for the diagnosis and pathogenesis of dry eye in menopausal women. Methods Six cynomolgus monkey were randomly divided into an experimental group and a control group (3 in each group). The experimental group underwent bilateral ovariectomy, while the control group underwent sham surgery with their ovaries reserved. Proteomic analysis was performed by LC-MS/MS on tears and serum collected from two groups. Differentially expressed proteins were identified and were performed cluster analysis, which included gene ontology, the Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction. Results 33 differentially expressed proteins have been identified in tears and17 differentially expressed proteins have been identified in serum. Kyoto Encyclopedia of Genes and Genomes enrichment analysis in tears has discovered Glucagon signaling pathway and neurotrophin signaling pathway may play an important role in the pathogenesis of dry eye. Gene ontology enrichment analysis in serum has discovered insulin-like growth factor binding and growth factor binding in molecular function probably make effort in pathogenesis of dry eye. KEGG analysis in serum has discovered salivary secretion may be the key pathway in pathogenesis of dry eye. Conclusions Protein G7PCH4, Q2PG17 and G7PT55 in tears may be the key protein in pathogenesis of dry eyes. Protein G7P1T1, G7PUN9 and G8F302 in serum may play an important role in pathogenesis of dry eyes.

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“…Neurotrophic factors and neurotrophins’ receptors enhance neuronal growth and survival [166,167] and play important roles in development, where they act as guidance cues for neurons. In the fully developed nervous system, they are involved in neuronal survival, synaptic plasticity and formation of long–lasting memories.…”

Section: Molecules and Pathways Involved In Pnimentioning

confidence: 99%

Nerves and Pancreatic Cancer: New Insights into A Dangerous Relationship

Gasparini

Pellegatta

Crippa

et al. 2019

Cancers

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Perineural invasion (PNI) is defined as the presence of neoplastic cells along nerves and/or within the different layers of nervous fibers: epineural, perineural and endoneural spaces. In pancreatic cancer—particularly in pancreatic ductal adenocarcinoma (PDAC)—PNI has a prevalence between 70 and 100%, surpassing any other solid tumor. PNI has been detected in the early stages of pancreatic cancer and has been associated with pain, increased tumor recurrence and diminished overall survival. Such an early, invasive and recurrent phenomenon is probably crucial for tumor growth and metastasis. PNI is a still not a uniformly characterized event; usually it is described only dichotomously (“present” or “absent”). Recently, a more detailed scoring system for PNI has been proposed, though not specific for pancreatic cancer. Previous studies have implicated several molecules and pathways in PNI, among which are secreted neurotrophins, chemokines and inflammatory cells. However, the mechanisms underlying PNI are poorly understood and several aspects are actively being investigated. In this review, we will discuss the main molecules and signaling pathways implicated in PNI and their roles in the PDAC.

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Neurotrophins and their involvement in digestive cancers

Cited by 51 publications

References 78 publications

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Proteomic analysis of tears and serum for dry eye disease using ovariectomized cynomolgus monkey

Nerves and Pancreatic Cancer: New Insights into A Dangerous Relationship

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