Gastrointestinal Stromal Tumors: From Molecular Pathogenesis to Therapy
Sherry X. Yang, Janet E. Dancey in Handbook of Therapeutic Biomarkers in Cancer, 2021
Exosomes originate from the fusion of endosomal multivesicular bodies (MVBs) [172], containing intraluminal vesicles (ILVs), with the plasma membrane and release of small bioactive vesicles via exocytosis into the interstitial space [173]. These vesicles are secreted by most cell types in vitro and in vivo. In addition, most cells of the immune system release exosomes, and includes B cells [174, 175] dendritic cells (DCs) [176], macrophages [177], T cells [178], and mast cells [179]. Furthermore, their presence in biological and physiological fluids, such as malignant ascites [180], bronchoalveolar lavage (BAL) fluid [181], serum [182], urine [183] and breast milk [184] has been well established. Even though the similar mechanisms lead to secretion of these vesicles, the molecular composition and function of these exosomes can vary in function of the cellular type that they derive from and the activation state of the parental cell [185, 186]. However, one invariant parameter is their density, morphology and size [186–188]. Exosome float on sucrose gradient to a density that ranges from 1.13 to 1.19 g/ml and display a circular shape with a diameter that varies from 30 to 100 nm [189].
Comparative Anatomy, Physiology, and Biochemistry of Mammalian Skin
David W. Hobson in Dermal and Ocular Toxicology, 2020
One of the most important and most numerous cells in the dermis is the fibroblast. They are usually found among the collagen fibers. Young fibroblasts have an abundance of cytoplasm while old fibroblasts (fibrocytes) have very little. In light microscopy, fibroblasts are spindle shaped with long cytoplasmic processes at each end. Their nucleus is oval and contains two to four nucleoli. Fibroblasts are motile and capable of mitosis. They are derived from mesenchymal cells. The fine structure of fibroblasts include elongated processes and the usual complement of organelles. The most characteristic feature in the cytoplasm is the abundance of rough endoplasmic reticulum. This is expected of cells that synthesize the collagen protein for export. Fine filaments, sometimes occurring in bundles, are usually seen in the cytoplasm of the fibroblasts. An active or young fibroblast showing extensive rough endoplasmic reticulum and several nucleoli indicates that it is synthesizing protein for secretion. Fibroblasts secrete procollagen, glycosaminoglycans, and proelastin. Secretory vesicles can be seen all along the cell membrane of the fibroblast. These vesicles fuse with the cell membrane and release their contents (procollagen) into the extracellular space where it will be enzymatically converted to collagen.38,199,204
Homeostasis of Dopamine
Nira Ben-Jonathan in Dopamine, 2020
All cells possess a constitutive secretory pathway whereby vesicles that originate in the Golgi complex contain newly synthesized proteins (i.e., enzymes, growth factors, receptors, and extracellular matrix components) and carry them to the cell surface. Once there, the vesicles contact the plasma membrane and either release their content to the cell exterior (e.g., hormones or neurotransmitters), or their enclosed proteins become embedded within the plasma membrane (e.g., receptors). Neurons and endocrine/neuroendocrine cells are highly specialized cells that are dedicated to intercellular communication and store their chemical signals in committed secretory vesicles. Upon receiving appropriate stimuli, these cells release their content to the cell exterior by a calcium-regulated exocytosis.
Modulating insulin secretion and inflammation against sodium arsenite toxicity by levosimendan as a novel pancreatic islets’ protector
Published in Toxin Reviews, 2023
Marzieh Daniali, Mona Navaei-Nigjeh, Maryam Baeeri, Soheyl Mirzababaei, Mahdi Gholami, Mahban Rahimifard, Mohammad Abdollahi
Regarding the insulin secretion pathway, it should be noted that insulin is produced in the endoplasmic reticulum and stored and transported in vesicles. Insulin is released from β-cells by exocytosis involving the attachment of secretory vesicles to the plasma membrane by a group of proteins called SNARE. The interaction of these proteins with the plasma membrane forms a stable complex that prepares the membrane for attachment and fusion to the granule. The exocytosis of vesicles is also regulated by Ca2+ concentration. Some studies also showed that as insulin granules become acidic, structural changes occur in the SNARE protein, facilitating its attachment to the membrane. By acting on the insulin gene transcription promoter, NaAsO2 toxin causes the cell to lose sensitivity to extracellular glucose concentrations and alter the stability of insulin mRNA, which is typically affected by glucose concentrations (Meloni et al.2013).
Cancer-associated fibroblasts and the tumor microenvironment in non-small cell lung cancer
Published in Expert Review of Anticancer Therapy, 2022
Jun Suzuki, Masahiro Tsuboi, Genichiro Ishii
Exosomes are membrane-enclosed secretory vesicles that are considered to be important mediators of intercellular communication. Luga et al. first showed that CAF-secreted exosomes promote protrusion, migration, and metastasis of breast cancer cells via canonical Wnt signaling [61]. Miki et al. found that exosomes secreted by CAFs cause migration and invasion of cancer cells in only the scirrhous type of gastric cancer [62]. Interestingly, it was the CD9+ exosome that was involved in this process, not the CD81+ exosome reported by Luga et al. Therefore, the role of exosomes secreted by CAFs may vary depending on the organs and expressed proteins. Exosomes contribute to the increased malignancy of cancer cells through non-coding microRNAs (miRNAs), proteins, and metabolites [63].
The secrets of protein secretion: what are the key features of comparative secretomics?
Published in Expert Review of Proteomics, 2020
To date, the major challenge of secretome characterization is the differentiation of actively secreted proteins from contaminants originating from cell culture medium or dead cells. Common approaches are simply based on the identification of ‘secreted’ proteins by shotgun MS, mRNA sequencing, or immunological detection (e.g. antibody arrays). Depending on whether the methods are robust against the identification of false-positives (contaminants), these approaches strongly depend on the prediction of protein secretion, which has been shown only to be accurate for classically secreted proteins [12,13]. Therefore, comparative secretomics was developed to allow the direct experimental identification of secreted proteins by omitting bioinformatic annotations as a decisive step. Comparative secretomics have shown to be robust and give access to high-confident data with a high proportion (>80%) of bona fide secreted proteins and a five-fold higher identification rate if consideration was not limited to proteins exclusively identified in the secretome [6]. Nevertheless, further research is necessary to better understand the composition of the secretome, because it depends on different criteria, such as cell type and culture condition. Further characterization of the high-confident secretome has revealed that proteins released by unconventional vesicle-mediated secretion processes are difficult to detect and that this protein group is not accessible without additional sample preparation protocols (unpublished data).
Related Knowledge Centers
- Enzyme
- Excretion
- Protein
- Toxin
- Cell Membrane
- Cell
- Gland
- Porosome
- Lipoprotein
- Bacterial Secretion System