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Purinergic Signalling Nov 2023Accumulating evidence supports the idea that cancer stem cells (CSCs) are those with the capacity to initiate tumors, generate phenotypical diversity, sustain growth,... (Review)
Review
Accumulating evidence supports the idea that cancer stem cells (CSCs) are those with the capacity to initiate tumors, generate phenotypical diversity, sustain growth, confer drug resistance, and orchestrate the spread of tumor cells. It is still controversial whether CSCs originate from normal stem cells residing in the tissue or cancer cells from the tumor bulk that have dedifferentiated to acquire stem-like characteristics. Although CSCs have been pointed out as key drivers in cancer, knowledge regarding their physiology is still blurry; thus, research focusing on CSCs is essential to designing novel and more effective therapeutics. The purinergic system has emerged as an important autocrine-paracrine messenger system with a prominent role at multiple levels of the tumor microenvironment, where it regulates cellular aspects of the tumors themselves and the stromal and immune systems. Recent findings have shown that purinergic signaling also participates in regulating the CSC phenotype. Here, we discuss updated information regarding CSCs in the purinergic system and present evidence supporting the idea that elements of the purinergic system expressed by this subpopulation of the tumor represent attractive pharmacological targets for proposing innovative anti-cancer therapies.
PubMed: 37966629
DOI: 10.1007/s11302-023-09976-5 -
Neuroscience Jul 2020Since the pioneering works of Ricardo Miledi, the neuromuscular junction represents the best example of a synapse where ACh is the neurotransmitter acting on nicotinic... (Review)
Review
Since the pioneering works of Ricardo Miledi, the neuromuscular junction represents the best example of a synapse where ACh is the neurotransmitter acting on nicotinic ACh receptors. ATP, co-released with ACh, is promptly degraded to Ado, which acts as a modulator of the cholinergic synaptic activity. Consequently, both ACh and adenosine play a crucial role in controlling the nerve-muscle communication. Apart from their role in the context of synaptic transmission, ACh and adenosine are autocrinally released by skeletal muscle cells, suggesting also a non nerve-driven function of these molecules. Indeed, the existence of cholinergic and adenosinergic systems has been widely described in many other non neuronal cell types. In this review, we will describe the two systems and their interplay in non-innervated differentiating skeletal muscle cells, and in innervated adult skeletal muscle fibers. We believe that the better comprehension of the interactions between the activity of nAChRs and adenosine could help the knowledge of skeletal muscle physiology. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
Topics: Acetylcholine; Cholinergic Agents; Muscle, Skeletal; Neuromuscular Junction; Synaptic Transmission
PubMed: 31121259
DOI: 10.1016/j.neuroscience.2019.05.020 -
Annals of the New York Academy of... Jun 1997Increasing evidence links the immune and endocrine systems. Cytokines produced by activated immune and immune accessory cells can affect, positively or negatively, the... (Review)
Review
Increasing evidence links the immune and endocrine systems. Cytokines produced by activated immune and immune accessory cells can affect, positively or negatively, the secretion of hormones from the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-ovarian axes. On the other hand, adrenal and ovarian hormones affect the secretion of cytokines by cells of the immune system. The interaction also occurs at a local level in paracrine or autocrine fashion. Cytokines produced by resident ovarian macrophages or ovarian cells can affect the follicle and the corpus luteum and, consequently, ovarian steroidogenesis at both phases of the menstrual cycle. Conversely, the ovarian steroids influence, positively or negatively, the secretion of cytokines from both the resident macrophages and local endocrine cells.
Topics: Cytokines; Endocrine Glands; Female; Humans; Immune System; Ovary
PubMed: 9238258
DOI: 10.1111/j.1749-6632.1997.tb52132.x -
Journal of Dermatological Science Feb 2000Biologically active nerve growth factor (NGF) is synthesised and released by proliferating normal human keratinocytes. NGF up-regulates the expression of NGF mRNA in... (Review)
Review
Biologically active nerve growth factor (NGF) is synthesised and released by proliferating normal human keratinocytes. NGF up-regulates the expression of NGF mRNA in keratinocytes. Keratinocytes express both the low (p75)- and the high-affinity (TrkA) NGF-receptors, which are located in the basal layer of the epidermis. K252, a specific inhibitor of trk phosphorylation, blocks NGF-induced keratinocyte proliferation, in absence of exogenous NGF. Normal keratinocytes over-expressing TrkA proliferate better than control transfectants, while the NGF mimicking anti-Trk antibody induces an increased keratinocyte proliferation in Trk over-expressing cells as compared to mock transfected keratinocytes. In addition, NGF over-expressing keratinocytes proliferate better than mock transfected cells. K252, by blocking TrkA phosphorylation, induces apoptosis in normal keratinocytes, but not in keratinocytes over-expressing bcl-2. Furthermore, NGF transfected keratinocytes are protected from UV-B-induced keratinocyte apoptosis, by maintaining constant levels of Bcl-2 and Bcl-xL . Taken together these results support the concept of an autocrine survival system sustained by NGF and its high-affinity receptor in human keratinocytes. Because NGF and Trk levels are highly expressed in psoriasis. one could speculate that NGF autocrine system plays a role in the mechanisms associated with this and other hyperproliferative skin conditions, including cancer.
Topics: Apoptosis; Autocrine Communication; Humans; Keratinocytes; Nerve Growth Factor
PubMed: 10674819
DOI: 10.1016/s0923-1811(99)00065-1 -
Journal of the National Cancer Institute Nov 2007Invasion is a defining hallmark of glioblastoma multiforme, just as metastasis characterizes other high-grade tumors. Glial tumors invariably recur due to the regrowth... (Review)
Review
Invasion is a defining hallmark of glioblastoma multiforme, just as metastasis characterizes other high-grade tumors. Glial tumors invariably recur due to the regrowth of invasive cells, which are unaffected by standard treatment modalities. Drivers of glioma invasion include autocrine signals propagated by secreted factors that signal through receptors on the tumor. These secreted factors are able to diffuse through the peritumoral stroma, thereby influencing parenchymal cells that surround the tumor mass. Here we describe various autocrine motility factors that are expressed by invasive glioma cells and explore the effects that they may have on normal cells present in the path of invasion. Conversely, normal brain parenchymal cells secrete ligands that can stimulate receptors on invasive glioma cells and potentially facilitate glioma invasion or create a permissive microenvironment for malignant progression. Parallel observations have been made for solid tumors of epithelial origin, in which parenchymal and stromal cells either support or suppress tumor invasion. Most autocrine and paracrine interactions involved in glioma invasion constitute known signaling systems in stages of central nervous system development that involve the migration of precursor cells that populate the developing brain. Key paracrine interactions between glioma cells and the brain microenvironment can influence glioma pathobiology and therefore contribute to its poor prognosis. Current therapies for glioma that could have an impact on paracrine communication between tumors and normal cells are discussed. We suggest that cells in the normal brain parenchyma be considered as potential targets for adjuvant therapies to control glioma growth because such cells are less likely to develop resistance than glioma cells.
Topics: Animals; Antineoplastic Agents; Astrocytes; Astrocytoma; Autocrine Communication; Axons; Brain Neoplasms; Glioblastoma; Glioma; Glucose-6-Phosphate Isomerase; Humans; Intercellular Signaling Peptides and Proteins; Neoplasm Invasiveness; Neoplastic Stem Cells; Neurons; Oligodendroglia; Paracrine Communication
PubMed: 17971532
DOI: 10.1093/jnci/djm187 -
Dental Update Nov 1992The centuries-old belief that stressed individuals are more susceptible to disease has gained scientific respectability in recent years. A new interdisciplinary science,... (Review)
Review
The centuries-old belief that stressed individuals are more susceptible to disease has gained scientific respectability in recent years. A new interdisciplinary science, psychoneuroimmunology (or as it is now more appropriately named, psychoneuroendocrinimmunology) has been born and, judging from the number of articles appearing annually, is thriving. In essence, stressors activate the neuroendocrine axis, which in turn influences the immune system. This is a bidirectional process, since chemicals are released by activated immunological cells which alter the functioning of the endocrine and autocrine nervous systems and influence our behaviour. This article examines these interactions.
Topics: Disease Susceptibility; Humans; Immune System; Neurosecretory Systems; Stress, Psychological
PubMed: 1306838
DOI: No ID Found -
The American Journal of Cardiology Dec 1987Recent data demonstrate that in addition to its conduit function, the blood vessel is an active synthetic and secretory organ containing several autocrine and paracrine...
Recent data demonstrate that in addition to its conduit function, the blood vessel is an active synthetic and secretory organ containing several autocrine and paracrine systems that are involved with the local regulation of its own function. The endothelium plays a pivotal role in modulating the balance between thrombogenesis and thrombolysis. In addition, it secretes vasorelaxant and vasoconstrictive substances, growth factors and inflammatory mediators that exert paracrine influences on vascular myocyte function. The vascular myocyte also expresses autocrine substances which influence its own function. The autocrine systems include angiotensin, prostaglandins, platelet-derived growth factor, insulin-like growth factor and heparin. These local factors exert modulatory influences on myocyte contractility and growth. It is conceivable that genetic or acquired abnormalities of one or several of these check and balance systems can result in increased vascular tone, generalized vascular hypertrophy or hyperplasia, or a combination, and contribute to the pathogenesis of hypertension. These autocrine-paracrine systems may be important targets for antihypertensive drug development.
Topics: Blood Platelets; Endothelium, Vascular; Growth Substances; Heparin; Hypertension; Muscle Contraction; Muscle, Smooth, Vascular; Neurotransmitter Agents; Renin-Angiotensin System; Vasomotor System
PubMed: 2891292
DOI: 10.1016/0002-9149(87)90468-1 -
Current Opinion in Cell Biology Apr 2020Physiological functions depend on a coordinated interplay of numerous different cell types. Proteins serve as major signaling molecules between cells; however, their... (Review)
Review
Physiological functions depend on a coordinated interplay of numerous different cell types. Proteins serve as major signaling molecules between cells; however, their comprehensive investigation in physiologically relevant settings has remained challenging. Mass spectrometry (MS)-based shotgun proteomics is emerging as a powerful technology for the systematic analysis of protein-mediated intercellular signaling and regulated post-translational modifications. Here, we discuss recent advancements in cell biological, chemical, and biochemical MS-based approaches for the profiling of cellular messengers released by sending cells, receptors expressed on the cell surface, and their interactions. We highlight methods tailored toward the mapping of dynamic signal transduction mechanisms at cellular interfaces and approaches to dissect communication cell specifically in heterocellular systems. Thereby, MS-based proteomics contributes a unique systems biology perspective for the identification of intercellular signaling pathways deregulated in disease.
Topics: Humans; Mass Spectrometry; Protein Processing, Post-Translational; Proteomics; Signal Transduction
PubMed: 31927463
DOI: 10.1016/j.ceb.2019.12.002 -
Clinical Science (London, England :... Sep 2012The RAS (renin-angiotensin system) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The... (Review)
Review
The RAS (renin-angiotensin system) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The major bioactive peptide of the system, AngII (angiotensin II), is neither synthesized in nor targets one specific organ. New research has identified additional peptides with important physiological and pathological roles. More peptides also mean newer enzymatic cascades that generate these peptides and more receptors that mediate their function. In addition, completely different roles of components that constitute the RAS have been uncovered, such as that for prorenin via the prorenin receptor. Complexity of the RAS is enhanced further by the presence of sub-systems in tissues, which act in an autocrine/paracrine manner independent of the endocrine system. The RAS seems relevant at the cellular level, wherein individual cells have a complete system, termed the intracellular RAS. Thus, from cells to tissues to the entire organism, the RAS exhibits continuity while maintaining independent control at different levels. The intracellular RAS is a relatively new concept for the RAS. The present review provides a synopsis of the literature on this system in different tissues.
Topics: Angiotensin II; Fibroblasts; Humans; Kidney; Muscle, Smooth, Vascular; Myocytes, Cardiac; Renin-Angiotensin System; Signal Transduction
PubMed: 22590974
DOI: 10.1042/CS20120089 -
Journal of Applied Physiology... Sep 2002This brief review presents the basic premises suggesting that insulin-like growth factor I (IGF-I), functioning in an autocrine/paracrine mode, is an important mediator... (Review)
Review
This brief review presents the basic premises suggesting that insulin-like growth factor I (IGF-I), functioning in an autocrine/paracrine mode, is an important mediator of skeletal muscle adaptation. Key intracellular signaling mechanisms associated with ligation of the primary IGF-I receptor are highlighted to illustrate the mechanisms by which IGF-I may promote muscle hypertrophy. In addition, a number of recent findings are presented that highlight the potential for interactions between IGF-I-related signaling pathways and intracellular signaling mechanisms activated by cytokines or hormonal systems.
Topics: Adaptation, Physiological; Animals; Autocrine Communication; Humans; Insulin; Insulin-Like Growth Factor I; Motor Activity; Muscle, Skeletal; Paracrine Communication; Signal Transduction
PubMed: 12183514
DOI: 10.1152/japplphysiol.01264.2001