Nearly 35 years ago when endosomal-derived extracellular vesicles were first identified in reticulocytes1, they were thought to essentially be garbage cans for the cell; removing cellular debris and marking it for degradation by lysosomes. After this discovery, these vesicles were identified in nearly all mammalian cell types, as well as in some eukaryotes and prokaryotes. However, the function of these molecular vehicles was not fully appreciated until 1996 when Raposo et al.2 revealed that B lymphocytes produce extracellular vesicles, termed exosomes, containing MHC II molecules on their surface that can stimulate antigen-specific T cells. By showing that exosomes have the ability to induce adative immune responses, Raposo et al. opened the door for studying the role that exosomes play in intercellular communication.
To clear up any nomenclature related confusion (since exosome has been used liberally to describe a wide variety of vesicles), when we say "exosome" we are refering to 40-100 nm vesicles that form when a protein, RNA, miRNA, or other cellular product is envaginated by an endosome, creating interluminal vesicles (ILVs). These newly formed multivesicular endosomes/bodies can then fuse with the plasma membrane of the cell, releasing the interluminal vesicles contained therein (which are now known as exosomes). The ILVs within the multivesicular body (MVB) could have a different fate, such as when the MVB fuses with a lyososome and the ILVs are degraded/recycled, but the term exosome refers specifcally to the ILVs that are secreted into the extracellualr space. While exsomes themselves contain proteins that are indicative of their parent cell, they also contain a set of proteins found in all exosomes, regardless of their tissue of origin. These proteins include tetraspanins (CD9, CD63, CD81, CD82), proteins that part of the ESCRT complex, and certain heat shock proteins (Hsp 60, Hsp 70, Hsp 90).
Recently, the role that exosomes play in cancer pathogenesis has come into view. Cancer-cell derived exosomes can promote tumor growth and metastasis through a variety of mechansism (a brief review of these mechanisms can be found here). Briefly, these mechaisms include shuttling of oncogenic proteins from tumor cells to surrounding cells, modulating the tumor microenvionrment to promote angiogenesis, altering distant sites to form pre-metastatic niches, and recruiting immune cells that promote tumor angiogenesis and growth. Given these pathological roles that exosomes play in tumorigenesis, exosomes are becoming a target of cancer therapy.
To aid in the important research regarding exosomes and cancer, Chondrex, Inc. has released with a new line of human monoclonal antibodies specific to exosome markers CD9 and CD63. In conjunction, we are also pleased to announce the release of mouse monoclonal antibodies specific for Programmed Death 1 (PD1) protein and PD-1 ligands. Both sets of antibodies are a part of our new line of products focused on cancer immunology.
Stay tuned for the release of our exosome isolation kits!