Cancer exacts a heavy socioeconomic cost. Earlier detection and treatment are likely to mitigate this cost. Unfortunately, conventional tissue biopsy, the gold standard in cancer diagnosis cannot fulfill the goal of e...Cancer exacts a heavy socioeconomic cost. Earlier detection and treatment are likely to mitigate this cost. Unfortunately, conventional tissue biopsy, the gold standard in cancer diagnosis cannot fulfill the goal of earlier detection. While liquid biopsy is a promising alternative to tissue biopsy, it has its challenges and limitations. A major challenge is the isolation of bona fide lipid membrane vesicles from biological fluids. In this review, we presented a new perspective of isolating different types of extracellular vesicles (EVs) by their affinity for membrane lipid binding ligands for liquid biopsy. EVs are lipid membrane particles naturally released by almost all cells and are found in almost all biological fluids suitable for liquid biopsy. They carry materials from the secreting cells that could affect the biology of the recipient cells and could thus inform on the state and progress of the disease. However, isolating bona fide EVs is a technical challenge as biological fluids have a complex composition and contain particles or aggregates that are physically similar to EVs. Here we review the use of membrane lipid-binding ligands to isolate different bona fide EV subtypes, and to circumvent the problem of co-isolating physically similar non-EV complexes in current EV isolation protocols. We will discuss the advantages of this technique and its potential for accelerated biomarker discovery and validation through examples of pre-clinical studies. We propose that isolating EV subtypes is a technically viable and robust strategy to overcome the current bottleneck of isolating EVs for liquid biopsy.展开更多
Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhanc...Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the cellular communication through the intercellular exchange of intact membrane patches, also called trogocytosis, which is a ubiquitous phenomenon. Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. It has been demonstrated that the membrane molecule transfer between immune cells such as dendritic and T cells can be derived through internalization/recycling pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Recent evidence implicates the trogocytosis as an important mechanism of the immune system to modulate immune responses. Exchange of membrane molecules/ antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we discuss the possible mechanisms of trogocytosis and its physiological relevance to immune system, with special reference to T cells and the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. Cellular & Molecular Immunology. 2008;5(4):261-269.展开更多
文摘Cancer exacts a heavy socioeconomic cost. Earlier detection and treatment are likely to mitigate this cost. Unfortunately, conventional tissue biopsy, the gold standard in cancer diagnosis cannot fulfill the goal of earlier detection. While liquid biopsy is a promising alternative to tissue biopsy, it has its challenges and limitations. A major challenge is the isolation of bona fide lipid membrane vesicles from biological fluids. In this review, we presented a new perspective of isolating different types of extracellular vesicles (EVs) by their affinity for membrane lipid binding ligands for liquid biopsy. EVs are lipid membrane particles naturally released by almost all cells and are found in almost all biological fluids suitable for liquid biopsy. They carry materials from the secreting cells that could affect the biology of the recipient cells and could thus inform on the state and progress of the disease. However, isolating bona fide EVs is a technical challenge as biological fluids have a complex composition and contain particles or aggregates that are physically similar to EVs. Here we review the use of membrane lipid-binding ligands to isolate different bona fide EV subtypes, and to circumvent the problem of co-isolating physically similar non-EV complexes in current EV isolation protocols. We will discuss the advantages of this technique and its potential for accelerated biomarker discovery and validation through examples of pre-clinical studies. We propose that isolating EV subtypes is a technically viable and robust strategy to overcome the current bottleneck of isolating EVs for liquid biopsy.
文摘Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the cellular communication through the intercellular exchange of intact membrane patches, also called trogocytosis, which is a ubiquitous phenomenon. Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. It has been demonstrated that the membrane molecule transfer between immune cells such as dendritic and T cells can be derived through internalization/recycling pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Recent evidence implicates the trogocytosis as an important mechanism of the immune system to modulate immune responses. Exchange of membrane molecules/ antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we discuss the possible mechanisms of trogocytosis and its physiological relevance to immune system, with special reference to T cells and the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. Cellular & Molecular Immunology. 2008;5(4):261-269.