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British Journal of Cancer May 2018Senescent cells activate genetic programmes that irreversibly inhibit cellular proliferation, but also endow these cells with distinctive metabolic and signalling... (Review)
Review
Senescent cells activate genetic programmes that irreversibly inhibit cellular proliferation, but also endow these cells with distinctive metabolic and signalling phenotypes. Although senescence has historically been considered a protective mechanism against tumourigenesis, the activities of senescent cells are increasingly being associated with age-related diseases, including cancer. An important feature of senescent cells is the secretion of a vast array of pro-inflammatory cytokines, chemokines, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Recent research has shown that SASP paracrine signalling can mediate several pro-tumourigenic effects, such as enhancing malignant phenotypes and promoting tumour initiation. In this review, we summarise the paracrine activities of senescent cells and their role in tumourigenesis through direct effects on growth and proliferation of tumour cells, tumour angiogenesis, invasion and metastasis, cellular reprogramming and emergence of tumour-initiating cells, and tumour interactions with the local immune environment. The evidence described here suggests cellular senescence acts as a double-edged sword in cancer pathogenesis, which demands further attention in order to support the use of senolytic or SASP-modulating compounds for cancer treatment.
Topics: Carcinogenesis; Cell Movement; Cell Proliferation; Cellular Reprogramming; Cellular Senescence; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Paracrine Communication
PubMed: 29670296
DOI: 10.1038/s41416-018-0066-1 -
American Journal of Physiology. Lung... Jun 2019Both physiological homeostasis and pathological disease processes in the lung typically result from complex, yet coordinated multicellular responses that are... (Review)
Review
Both physiological homeostasis and pathological disease processes in the lung typically result from complex, yet coordinated multicellular responses that are synchronized via paracrine and endocrine intercellular communication pathways. Of late, extracellular vesicles have emerged as important information shuttles that can coordinate and disseminate homeostatic and disease signals. In parallel, extracellular vesicles in biological fluids such as sputum, mucus, epithelial lining fluid, edema fluid, the pulmonary circulation, pleural fluid, and lymphatics have emerged as promising candidate biomarkers for diagnosis and prognosis in lung disease. Extracellular vesicles are small, subcellular, membrane-bound vesicles containing cargos from parent cells such as lipids, proteins, genetic information, or entire organelles. These cargos endow extracellular vesicles with biologically active information or functions by which they can reprogram their respective target cells. Recent studies show that extracellular vesicles found in lung-associated biological fluids play key roles as biomarkers and effectors of disease. Conversely, administration of naïve or engineered extracellular vesicles with homeostatic or reparative effects may provide a promising novel protective and regenerative strategy to treat lung disease. To highlight this rapidly developing field, the is now launching a special Call for Papers on extracellular vesicles in lung health, disease, and therapy. This review aims to set the stage for this call by introducing extracellular vesicles and their emerging roles in lung physiology and pathobiology.
Topics: Biomarkers; Endocrine System; Extracellular Vesicles; Humans; Lung; Lung Diseases; Paracrine Communication; Prognosis
PubMed: 30892076
DOI: 10.1152/ajplung.00546.2018 -
Journal of Gastroenterology and... Aug 2013Cholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are... (Review)
Review
Cholangiocytes are involved in a variety of processes essential for liver pathophysiology. To meet their demanding metabolic and functional needs, bile ducts are nourished by their own arterial supply, the peribiliary plexus. This capillary network originates from the hepatic artery and is strictly arranged around the intrahepatic bile ducts. Biliary and vascular structures are linked by a close anatomic and functional association necessary for liver development, normal organ physiology, and liver repair. This strong association is finely regulated by a range of angiogenic signals, enabling the cross talk between cholangiocytes and the different vascular cell types. This review will briefly illustrate the "vascular" properties of cholangiocytes, their underlying molecular mechanisms and the relevant pathophysiological settings.
Topics: Angiopoietins; Animals; Autocrine Communication; Bile Duct Diseases; Bile Ducts, Intrahepatic; Epithelial Cells; Epithelium; Humans; Liver; Liver Diseases, Alcoholic; Liver Regeneration; Neovascularization, Pathologic; Paracrine Communication; Platelet-Derived Growth Factor; Rats; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 23855292
DOI: 10.1111/jgh.12022 -
International Journal of Oncology Jun 2014Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific... (Review)
Review
Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific stem cells to rebuild damaged tissue and cancer stem cells to initiate and promote cancer. Mesenchymal stem cells, attracted to wounds and cancer, facilitate wound healing and support cancer progression primarily by secreting bioactive factors. There is now growing evidence that, like mesenchymal stem cells, also tissue-specific and cancer stem cells manipulate their environment by paracrine actions. Soluble factors and microvesicles released by these stem cells have been shown to protect recipient cells from apoptosis and to stimulate neovascularization. These paracrine mechanisms may allow stem cells to orchestrate wound healing and cancer progression. Hence, understanding these stem cell-driven paracrine effects may help to improve tissue regeneration and cancer treatment.
Topics: Animals; Apoptosis; Humans; Mesenchymal Stem Cells; Neoplasms; Neoplastic Stem Cells; Neovascularization, Pathologic; Organ Specificity; Paracrine Communication; Signal Transduction; Wound Healing
PubMed: 24728412
DOI: 10.3892/ijo.2014.2385 -
BioMed Research International 2021When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of...
BACKGROUND
When vascular endothelial cells are subjected to external stimuli, paracrine hormones and cytokines act on adjacent cells. The regulation of the biological behaviour of cells is closely related to the maintenance of organ function and the occurrence and development of disease. However, it is unclear whether vascular endothelial cells affect the biological behaviour of cells involved in wound repair through autocrine and paracrine mechanisms and ultimately play a role in wound healing. We aimed to verify the effect of the autocrine and paracrine functions of vascular endothelial cells on wound healing.
MATERIALS AND METHODS
ELISA was used to detect platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor in human umbilical vascular endothelial cell-conditioned medium (HUVEC-CM). Different concentrations of HUVEC-CM were used to treat different stem cells. CCK-8 and scratch assays were used to detect the proliferation and migration ability of each cell. A full-thickness dorsal skin defect model was established in mice, and skin wound healing was observed after the local injection of HUVEC-CM, endothelial cell medium (ECM), or normal saline. H&E staining and immunofluorescence were used to observe the gross morphology of the wound tissue, the epithelial cell migration distance, and the expression of CD3 and CD31.
RESULTS
HUVEC-CM promotes the proliferation and migration of epidermal stem cells, skin fibroblasts, bone marrow mesenchymal stem cells, and HUVECs themselves. Furthermore, HUVEC-CM can promote angiogenesis in mouse skin wounds and granulation tissue formation and can accelerate wound surface epithelialization and collagen synthesis, thereby promoting wound healing.
CONCLUSION
Our results clearly suggest that it is practicable and effective to promote wound healing with cytokines secreted by vascular endothelial cells in a mouse model.
Topics: Antigens, CD; Autocrine Communication; Biomarkers; Cell Movement; Cell Proliferation; Culture Media, Conditioned; Cytokines; Fibroblasts; Human Embryonic Stem Cells; Human Umbilical Vein Endothelial Cells; Humans; Mesenchymal Stem Cells; Paracrine Communication; Skin; Wound Healing
PubMed: 33937411
DOI: 10.1155/2021/6695663 -
Cell Transplantation 2020Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation... (Review)
Review
Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation ability of MSCs was believed to be primarily responsible for tissue repair. Recent studies have shown that paracrine mechanisms play an important role in this process. MSCs can secrete soluble molecules and extracellular vesicles (EVs), which mediate paracrine communication. EVs contain large amounts of proteins and nucleic acids, such as mRNAs and microRNAs (miRNAs), and can transfer the cargo between cells. The cargoes are similar to those in MSCs and are not susceptible to degradation due to the protection of the EV bimolecular membrane structure. MSC-EVs can mimic the biological characteristics of MSCs, such as differentiation, maturation, and self-renewal. Due to their broad biological functions and their ability to transfer molecules between cells, EVs have been intensively studied by an increasing number of researchers with a focus on therapeutic applications, especially those of EVs secreted by MSCs. In this review, we discuss MSC-derived EVs and their therapeutic potential in tissue regeneration.
Topics: Cell Differentiation; Extracellular Vesicles; Humans; Mesenchymal Stem Cells; MicroRNAs; Paracrine Communication; Regenerative Medicine
PubMed: 32207341
DOI: 10.1177/0963689720908500 -
Molecular Immunology Apr 2017Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide... (Review)
Review
Most of the complement proteins in circulation are, by and large, synthesized in the liver. However data accumulated over the past several decades provide incontrovertible evidence that some if not most of the individual complement proteins are also synthesized extrahepatically by activated as well as non-activated cells. The question that is finally being addressed by various investigators is: are the locally synthesized proteins solely responsible for the myriad of biological functions in situ without the contribution of systemic complement? The answer is probably "yes". Among the proteins that are synthesized locally, C1q takes center stage for several reasons. First, it is synthesized predominantly by potent antigen presenting cells such as monocytes, macrophages and dendritic cells (DCs), which by itself is a clue that it plays an important role in antigen presentation and/or DC maturation. Second, it is transiently anchored on the cell surface via a transmembrane domain located in its A chain before it is cleaved off and released into the pericellular milieu. The membrane-associated C1q in turn, is able to sense danger patterns via its versatile antigen-capturing globular head domains. More importantly, locally synthesized C1q has been shown to induce a plethora of biological functions through the induction of immunomodulatory molecules by an autocrine- or paracrine- mediated signaling in a manner that mimics those of TNFα. These include recognition of pathogen- and danger- associated molecular patterns, phagocytosis, angiogenesis, apoptosis and induction of cytokines or chemokines that are important in modulating the inflammatory response. The functional convergence between C1q and TNFα in turn is attributed to their shared genetic ancestry. In this paper, we will infer to the aforementioned "local-synthesis-for-local function" paradigm using as an example, the role played by locally synthesized C1q in autoimmunity in general and in systemic lupus erythematosus in particular.
Topics: Animals; Autocrine Communication; Complement C1q; Dendritic Cells; Humans; Immune Tolerance; Paracrine Communication
PubMed: 27914690
DOI: 10.1016/j.molimm.2016.11.003 -
Current Opinion in Hematology May 2014This review identifies recent advances in the field of vascular repair by regenerative endothelial cells and endothelial progenitor cells (EPCs). (Review)
Review
PURPOSE OF REVIEW
This review identifies recent advances in the field of vascular repair by regenerative endothelial cells and endothelial progenitor cells (EPCs).
RECENT FINDINGS
A growing number of studies indicate that bone marrow-derived circulating EPCs do not engraft into blood vessels, but that such circulating cells may regulate vascular repair via paracrine mechanisms. Novel modes of paracrine regulation are being uncovered, such as the release of endothelial cell-derived microparticles or microvesicles that contain microRNAs which can promote vascular repair. Instead of circulating cells, tissue-resident endothelial cells or EPCs may primarily drive the restoration of vascular function after endothelial injury. In addition to the generation of endothelial cells/EPCs from pluripotent stem cells, direct reprogramming of fibroblasts to endothelial cells/EPCs is becoming an important source of regenerative vascular cells.
SUMMARY
Ongoing efforts to understand the mechanisms that regulate vascular repair by resident regenerative vascular cells as well as their generation from fibroblasts and pluripotent stem cells will form the basis of future regenerative therapies.
Topics: Blood Vessels; Endothelial Cells; Endothelium, Vascular; Humans; Paracrine Communication; Regeneration; Stem Cell Transplantation; Stem Cells
PubMed: 24637956
DOI: 10.1097/MOH.0000000000000041 -
Advanced Healthcare Materials Apr 2021Mesenchymal stem cells (MSCs) have been widely studied as a versatile cell source for tissue regeneration and remodeling due to their potent bioactivity, which includes... (Review)
Review
Mesenchymal stem cells (MSCs) have been widely studied as a versatile cell source for tissue regeneration and remodeling due to their potent bioactivity, which includes modulation of inflammation response, macrophage polarization toward proregenerative lineage, promotion of angiogenesis, and reduction in fibrosis. This review focuses on profiling the effects of paracrine signals of MSCs, commonly referred to as the secretome, and highlighting the various engineering approaches to tune the MSC secretome. Recent advances in biomaterials-based therapeutic strategies for delivery of MSCs and MSC-derived secretome in the form of extracellular vesicles are discussed, along with their advantages and challenges.
Topics: Extracellular Vesicles; Fibrosis; Humans; Mesenchymal Stem Cells; Paracrine Communication; Wound Healing
PubMed: 33433956
DOI: 10.1002/adhm.202001689 -
BioEssays : News and Reviews in... Jan 2015Recent findings in several organ systems show that cytoneme-mediated signaling transports signaling proteins along cellular extensions and targets cell-to-cell exchanges... (Review)
Review
Recent findings in several organ systems show that cytoneme-mediated signaling transports signaling proteins along cellular extensions and targets cell-to-cell exchanges to synaptic contacts. This mechanism of paracrine signaling may be a general one that is used by many (or all) cell types in many (or all) organs. We briefly review these findings in this perspective. We also describe the properties of several signaling systems that have previously been interpreted to support a passive diffusion mechanism of signaling protein dispersion, but can now be understood in the context of the cytoneme mechanism. Also watch the Video Abstract.
Topics: Animals; Cell Communication; Diffusion; Extracellular Matrix; Humans; Models, Biological; Paracrine Communication; Signal Transduction
PubMed: 25476066
DOI: 10.1002/bies.201400122