Neuropeptide Y/Y5 Receptor Pathway Stimulates Neuroblastoma Cell Motility Through RhoA Activation

Abualsaud, Nouran; Caprio, Lindsay; Galli, Susana; Krawczyk, Ewa; Alamri, Lamia; Zhu, Su‐Li; Gallicano, G. Ian; Kitlińska, Joanna

doi:10.3389/fcell.2020.627090

Cited by 10 publications

(10 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the highest concentration of NPY, saxagliptin administration restored the migration capacity of fibroblasts. Interestingly, in other cell types, NPY has been shown to stimulate migration of human umbilical endothelial cells [ 68 ], to promote ischemic angiogenesis and vascularization in the rat ischemic hind limb [ 69 ], and to increase motility of neuroblastoma cells [ 70 ]. Our finding suggests that NPY might act differently on cardiac fibroblasts, reducing their migration and likely preventing cardiac fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Saxagliptin Cardiotoxicity in Chronic Heart Failure: The Role of DPP4 in the Regulation of Neuropeptide Tone

et al. 2022

View full text Add to dashboard Cite

Dipeptidyl-peptidase-4 (DPP4) inhibitors are novel medicines for diabetes. The SAVOR-TIMI-53 clinical trial revealed increased heart-failure-associated hospitalization in saxagliptin-treated patients. Although this side effect could limit therapeutic use, the mechanism of this potential cardiotoxicity is unclear. We aimed to establish a cellular platform to investigate DPP4 inhibition and the role of its neuropeptide substrates substance P (SP) and neuropeptide Y (NPY), and to determine the expression of DDP4 and its neuropeptide substrates in the human heart. Western blot, radio-, enzyme-linked immuno-, and RNA scope assays were performed to investigate the expression of DPP4 and its substrates in human hearts. Calcein-based viability measurements and scratch assays were used to test the potential toxicity of DPP4 inhibitors. Cardiac expression of DPP4 and NPY decreased in heart failure patients. In human hearts, DPP4 mRNA is detectable mainly in cardiomyocytes and endothelium. Treatment with DPP4 inhibitors alone/in combination with neuropeptides did not affect viability but in scratch assays neuropeptides decreased, while saxagliptin co-administration increased fibroblast migration in isolated neonatal rat cardiomyocyte-fibroblast co-culture. Decreased DPP4 activity takes part in the pathophysiology of end-stage heart failure. DPP4 compensates against the elevated sympathetic activity and altered neuropeptide tone. Its inhibition decreases this adaptive mechanism, thereby exacerbating myocardial damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Saxagliptin Cardiotoxicity in Chronic Heart Failure: The Role of DPP4 in the Regulation of Neuropeptide Tone

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Neurons [121] Pancreatic β cells [122] Vascular smooth muscle cells [123] Monocytes [123] Macrophages [123] Enterocytes [123] Endothelial cells [121] Langerhans cells [123] Microglia [123] B & T lymphocytes [123] Neurons [121] Monocytes [123] Macrophages [122,123] Lymphocytes [123] Dendritic Cells [123] Neutrophils [123] B & T Lymphocytes [123] Leukocytes [123] Microglia [123] Osteoblasts [122] Endothelial Cells [122] PDL Stem Cells [105] Proposed to be involved in initiation and regulation of periodontitis [105] Reduced levels observed in diseased sites of periodontitis patients [96] High levels observed in the saliva of periodontitis patients [124] Promotion of osteogenesis [105] Increase in PDL stem cells' osteogenic capacity in vitro [125] Pituitary Adenylate Cyclase-Activating Peptide (PACAP)…”

Section: Role Of Sensory Neuropeptides In Pain and Inflammationmentioning

confidence: 99%

Nociceptor–Macrophage Interactions in Apical Periodontitis: How Biomolecules Link Inflammation with Pain

Menon,

Kishen

2023

Biomolecules

View full text Add to dashboard Cite

Periradicular tissues have a rich supply of peripheral afferent neurons, also known as nociceptive neurons, originating from the trigeminal nerve. While their primary function is to relay pain signals to the brain, these are known to be involved in modulating innate and adaptive immunity by initiating neurogenic inflammation (NI). Studies have investigated neuroanatomy and measured the levels of biomolecules such as cytokines and neuropeptides in human saliva, gingival crevicular fluid, or blood/serum samples in apical periodontitis (AP) to validate the possible role of trigeminal nociceptors in inflammation and tissue regeneration. However, the contributions of nociceptors and the mechanisms involved in the neuro-immune interactions in AP are not fully understood. This narrative review addresses the complex biomolecular interactions of trigeminal nociceptors with macrophages, the effector cells of the innate immune system, in the clinical manifestations of AP.

show abstract

“…[ 120 ] Strongly inducible Y5 expression was found in migratory cells of neuroblastoma [ 120 ] and liver cancer. [ 121 ] Together, it appears that NPY receptors follow four general principles: 1) NPY receptors are mainly expressed in specific endocrine tumors, epithelial malignancies, and embryonal tumors [ 122 ] ; 2) tumor cells express predominantly Y1 and/or Y2 subtypes [ 117 ] ; 3) Y1 receptors are mainly involved in the modulation of cancer cell proliferation, whereas Y2 receptor activation appears to promote angiogenesis [ 123 ] ; and 4) Y5 receptors regulate cell proliferation, [ 124 ] chemotactic migration, invasion, [ 120,121 ] and contribute to chemoresistance. [ 120 ] These properties make NPY receptors particularly appealing as potential targets for cancer imaging and treatment.…”

Section: Neuropeptides and Their Receptors In Cancermentioning

confidence: 99%

“…[ 121 ] Together, it appears that NPY receptors follow four general principles: 1) NPY receptors are mainly expressed in specific endocrine tumors, epithelial malignancies, and embryonal tumors [ 122 ] ; 2) tumor cells express predominantly Y1 and/or Y2 subtypes [ 117 ] ; 3) Y1 receptors are mainly involved in the modulation of cancer cell proliferation, whereas Y2 receptor activation appears to promote angiogenesis [ 123 ] ; and 4) Y5 receptors regulate cell proliferation, [ 124 ] chemotactic migration, invasion, [ 120,121 ] and contribute to chemoresistance. [ 120 ] These properties make NPY receptors particularly appealing as potential targets for cancer imaging and treatment.…”

Section: Neuropeptides and Their Receptors In Cancermentioning

confidence: 99%

Neuropeptides in Cancer: Friend and Foe?

Berisha

Borniger

2022

Advanced Biology

View full text Add to dashboard Cite

highly dynamic network of various cell types (e.g., cancer cells, endothelial cells, immune cells, fibroblasts) that exert differential effects on neuronal activity within the local environment. Thus, complex signaling between cancer and stromal cells in the TME results in altered firing rates of local nerves. Reciprocally, increased neuronal activity and subsequent release of classical neurotransmitters and/or neuropeptides within the TME results in enhanced cancer progression and subsequent metastasis in various preclinical models and clinical studies. [5][6][7][8][9] Nerves interact with multiple stromal cells in the TME where they indirectly promote tumor growth, progression, and subsequent metastasis. [10] Several studies have demonstrated that sympathetic nerve innervation and subsequent release of the neurotransmitter norepinephrine (NE) is increased in breast tumors. [6,8,9] However, recent work has demonstrated that there is an inverse relationship between tumor weight and norepinephrine content (i.e., larger the size of the tumor, the lower the levels of NE), despite increased innervation of sympathetic nerves within the TME. [11] These findings may be attributed to a relatively unexplored phenomenon: neuropeptide release within the TME. Neuropeptides are molecular messengers that regulate a variety of functions in the central and peripheral nervous systems via binding G-protein-coupled receptors (GPCRs) on target cells. One of the many functions of neuropeptides is serving as growth factors for normal cells via the activation of the heterotrimeric G protein Gq and subsequent synthesis of second messengers and engagement of tyrosine phosphorylation cascades. Neuropeptides act as neuromodulators, in that they can alter the response of neurons to neurotransmitters and other circulating signals, such as leptin, ghrelin, glucose, and insulin-all of which are affected during cancer progression. [12][13][14][15][16][17] For example, both neuropeptide Y (NPY) and hypocretin/orexin neurons appear to mediate some of the orexigenic effects of centrally administered ghrelin as administration of NPY receptor antagonists attenuated ghrelininduced feeding. Similarly, ghrelin-induced feeding was suppressed in orexin knockout mice, indicating that ghrelin may stimulate feeding through both the orexin and NPY systems. [18] However, neuropeptide signaling is exploited within cancer cells and many studies demonstrate the contribution of neuropeptides in tumor cell proliferation and migration, [19] with many major neuropeptides also potentially contributing to cancer processes (see Table 1). Additionally, neuropeptides exert direct Neuropeptides are small regulatory molecules found throughout the body, most notably in the nervous, cardiovascular, and gastrointestinal systems. They serve as neurotransmitters or hormones in the regulation of diverse physiological processes. Cancer cells escape normal growth control mechanisms by altering their expression of growth factors, receptors, or intracellular signals, and neuropeptid...

show abstract

Neuropeptide Y/Y5 Receptor Pathway Stimulates Neuroblastoma Cell Motility Through RhoA Activation

Cited by 10 publications

References 42 publications

Saxagliptin Cardiotoxicity in Chronic Heart Failure: The Role of DPP4 in the Regulation of Neuropeptide Tone

Saxagliptin Cardiotoxicity in Chronic Heart Failure: The Role of DPP4 in the Regulation of Neuropeptide Tone

Nociceptor–Macrophage Interactions in Apical Periodontitis: How Biomolecules Link Inflammation with Pain

Neuropeptides in Cancer: Friend and Foe?

Contact Info

Product

Resources

About