The role of TRKA signaling in IL-10 production by apoptotic tumor cell-activated macrophages

Ley, Stephanie; Weigert, Andreas; Weichand, Benjamin; Henke, Nina; Mille-Baker, Blandine; Janssen, Richard A. J.; Brüne, Bernhard

doi:10.1038/onc.2012.77

Cited by 35 publications

(30 citation statements)

References 40 publications

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“…The link between inflammation and cancer involves a variety of cytokines and chemokines and NGF is produced by various immune cells (Leon et al ., 1994; Nilsson et al ., 1997). It has recently been shown that breast cancer NGF can stimulate TrkA signaling in tumor-associated macrophages, increasing IL-10 production (Ley et al ., 2013). …”

Section: Neurotrophin-induced Neurogenesis In Tumor Tissuesmentioning

confidence: 99%

NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling

Bradshaw

Pundavela

Biarc

et al. 2015

Advances in Biological Regulation

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Nerve growth factor (NGF) and its precursor (proNGF) are primarily considered as regulators of neuronal function that induce their responses via the tyrosine kinase receptor TrkA and the pan-neurotrophin receptor p75NTR. It has been generally held that NGF exerts its effects primarily through TrkA, inducing a cascade of tyrosine kinase-initiated responses, while proNGF binds more strongly to p75NTR. When this latter entity interacts with a third receptor, sortilin, apoptotic responses are induced in contrast to the survival/differentiation associated with the other two. Recent studies have outlined portions of the downstream phosphoproteome of TrkA in the neuronal PC12 cells and have clarified the contribution of individual docking sites in the TrkA endodomain. The patterns observed showed a similarity with the profile induced by the epidermal growth factor receptor, which is extensively associated with oncogenesis. Indeed, as with other neurotrophic factors, the distribution of TrkA and p75NTR is not limited to neuronal tissue, thus providing an array of targets outside the nervous systems. One such source is breast cancer cells, in which NGF and proNGF stimulate breast cancer cell survival/growth and enhance cell invasion, respectively. This latter activity is exerted via TrkA (as opposed to p75NTR) in conjunction with sortilin. Another tissue overexpressing proNGF is prostate cancer and here the ability of cancer cells to induce neuritogenesis has been implicated in cancer progression. These studies show that the non-neuronal functions of proNGF/NGF are likely integrated with their neuronal activities and point to the clinical utility of these growth factors and their receptors as biomarkers and therapeutic targets for metastasis and cancer pain.

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Section: Neurotrophin-induced Neurogenesis In Tumor Tissuesmentioning

confidence: 99%

NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling

Bradshaw

Pundavela

Biarc

et al. 2015

Advances in Biological Regulation

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“…It has been proposed that S1P secreted by dying cells activates S1P receptors in surrounding macrophages, inducing tyrosine kinase receptor A (TRKA) shuttling to the plasma membrane. The activation of TRKA by cancer cell-derived nerve growth factor, leads to interleukin 10 production, turning on the switch toward immunosuppressive macrophages [131]. However, it is also possible that S1P in developing tumors comes from growing cancer cells with increasingly dysregulated S1P metabolism.…”

Section: S1p Metabolism and Transportmentioning

confidence: 99%

Shaping the landscape: Metabolic regulation of S1P gradients

Olivera

Allende

Proia

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Sphingosine-1-phosphate (S1P) is a lipid that functions as a metabolic intermediate and a cellular signaling molecule. These roles are integrated when compartments with differing extracellular S1P concentrations are formed that serve to regulate functions within the immune and vascular systems, as well as during pathologic conditions. Gradients of S1P concentration are achieved by the organization of cells with specialized expression of S1P metabolic pathways within tissues. S1P concentration gradients underpin the ability of S1P signaling to regulate in vivo physiology. This review will discuss the mechanisms that are necessary for the formation and maintenance of S1P gradients, with the aim of understanding how a simple lipid controls complex physiology.

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“…TAMs present a defective TLR response caused by tumour-selective disruption of the MyD88 signalling cascade, and affect the TIR-domain-containing adapter-inducing interferon-β (TRIF)/TNF receptor associated factors (TRAF3)-dependent pathway in their own favour, leading to favourable transcription at the IL-10 promoter region [62]. In the presence of apoptotic tumour cell-factors like sphingosine-1-phosphate (S1P), TAMs use tyrosine kinase receptor A (TRKA), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and MAPK signalling to induce IL-10 [63]. …”

Section: Introductionmentioning

confidence: 99%

Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

et al. 2017

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BackgroundOral squamous cell carcinoma (OSCC) accounts over 90% of malignant neoplasms of the oral cavity. This pathological entity is associated to a high mortality rate that has remained unchanged over the past decades. Tumour-associated macrophages (TAMs) are believed to have potential involvement in OSCC progression. However, the molecular networks involved in communication between stroma and cancer cells have not yet been fully elucidated.Main bodyThe role of M2 polarized cells in oral carcinogenesis is supported by a correlation between TAMs accumulation into OSCC stroma and poor clinical outcome. Signalling pathways such as the NF-κB and cytokines released in the tumour microenvironment promote a bidirectional cross-talk between M2 and OSCC cells. These interactions consequently result in an increased proliferation of malignant cells and enhances aggressiveness, thus reducing patients’ survival time.ConclusionsHere, we present a comprehensive review of the role of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10 and the receptor tyrosine kinase Axl in macrophage polarization to an M2 phenotype and OSCC progression. Understanding the molecular basis of oral carcinogenesis and metastatic spread of OSCC would promote the development of targeted treatment contributing to a more favourable prognosis.

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The role of TRKA signaling in IL-10 production by apoptotic tumor cell-activated macrophages

Cited by 35 publications

References 40 publications

NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling

NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling

Shaping the landscape: Metabolic regulation of S1P gradients

Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

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