Exosomes, extracellular vesicles originating from endosomes, were discovered in the late 1980s and their function in intercellular communication has since garnered considerable interest. Exosomes are lipid bilayer-coated vesicles that range in size from 30 to 150 nm and appear as sacs under the electron microscope. Exosome secretion is crucial for cell-to-cell contact in both normal physiology and the development and spread of tumors. Furthermore, cancer cells can secrete more exosomes than normal cells. Scientists believe that intercellular communication in the complex tissue environment of the human body is an important reason for cancer cell invasion and metastasis. For example, some particles containing regulatory molecules are secreted in the tumor microenvironment, including exosomes. Then the contents of exosomes can be released by donor cells into the environment and interact with recipient cells to promote the migration and invasion of tumor cells. Therefore, in this review, we summarized the biogenesis of exosome, as well as exosome cargo and related roles. More importantly, this review introduces and discusses the factors that have been reported to affect exosome secretion in tumors and highlights the important role of exosomes in tumors.

Exosomes carry and transmit signaling molecules used for intercellular communication. The generation and secretion of exosomes is a multistep interlocking process that allows simultaneous control of multiple regulatory sites. Protein molecules, mainly RAB GTPases, cytoskeletal proteins and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE), are specifically regulated in response to pathological conditions such as altered cellular microenvironment, stimulation by pathogenic factors, or gene mutation. This interferes with the smooth functioning of endocytosis, translocation, degradation, docking and fusion processes, leading to changes in the secretion of exosomes. Large numbers of secreted exosomes are disseminated by the flow of body fluids and absorbed by the recipient cells. By transmitting characteristic functional proteins and genetic information produced under disease conditions, exosomes can change the physiological state of the recipient cells and their microenvironment. The microenvironment, in turn, affects the occurrence and development of disease. Therefore, this review will discuss the mechanism by which exosome secretion is regulated in cells following the formation of mature secretory multivesicular bodies (MVBs). The overall aim is to find ways to eliminate disease-derived exosomes at their source, thereby providing an important new basis for the clinical treatment of disease.

Pancreatic cancer is one of the most lethal neoplasms with high metastatic potential and is resistant to almost all current therapies. Epalrestat is an aldo-keto reductase family 1 member B1 (AKR1B1) inhibitor for the treatment of diabetic neuropathy, but its potential application in cancer treatment and the underlying mechanism are largely unknown. Here, we found that AKR1B1 is upregulated in pancreatic cancer and is positively associated with metastasis. Upregulated AKR1B1 promoted exosome secretion, accelerating cell migration in pancreatic cancer cells. Further analysis indicated that AKR1B1 negatively regulated lysosomal function and multivesicular body (MVB) degradation in lysosomes. However, AKR1B1 had a minimal role in the generation of MVBs. Transcription factor EB (TFEB) and MVB-expressed RAB7A were two molecular targets that are negatively regulated by AKR1B1. These results uncovered a critical role for AKR1B1 in the regulation of lysosomal function and exosome secretion. Pharmacological targeting of AKR1B1 by clinically used medicines, such as Epalrestat, might represent an efficient way to inhibit pancreatic growth and metastasis.