Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance

Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance

2019 | Ladan Mashouri, Hassan Yousefi, Amir Reza Aref, Ali Mohammad Ahadi, Fatemeh Molaei, Suresh K. Alahari
Exosomes are small membrane-bound vesicles that play a critical role in cancer progression, including metastasis and drug resistance. They are produced by various cell types, including tumor cells, and contain a variety of biomolecules such as proteins, lipids, and nucleic acids. Exosomes facilitate intercellular communication by transferring these cargoes to recipient cells, where they can influence cellular behavior. In cancer, exosomes contribute to tumor microenvironment (TME) remodeling, angiogenesis, and epithelial-mesenchymal transition (EMT), which are essential for tumor growth and metastasis. Additionally, exosomes can promote drug resistance by transferring resistance-related molecules to cancer cells, making them more resistant to chemotherapy and other treatments. Exosome biogenesis involves the formation of intraluminal vesicles (ILVs) within multivesicular bodies (MVBs), which are then released into the extracellular space. This process is regulated by various proteins, including the ESCRT machinery, and can be either ESCRT-dependent or ESCRT-independent. Exosomes are composed of a complex mixture of proteins, lipids, and nucleic acids, which reflect the donor cell's characteristics. The lipid composition of exosomes is also cell-specific and plays a role in their biogenesis and function. Tumor-derived exosomes (TDEs) play a significant role in tumor progression by promoting angiogenesis, invasion, and metastasis. They can induce EMT, which enhances the invasive and metastatic potential of cancer cells. TDEs also contribute to therapy resistance by transferring resistance-related molecules to cancer cells, enabling them to survive and proliferate despite treatment. Additionally, TDEs can modulate the tumor microenvironment by influencing immune cells and promoting the formation of a pre-metastatic niche. Exosomes have potential applications in cancer therapy, including targeted drug delivery and immunotherapy. They can be engineered to deliver therapeutic agents such as chemotherapeutic drugs, functional RNAs, and proteins to cancer cells. Exosomes can also be used to modulate the tumor microenvironment and enhance the immune response against cancer. However, challenges remain in the clinical application of exosome-based therapies, including the need for further research to optimize their targeting and therapeutic efficacy. Understanding the mechanisms of exosome biogenesis, function, and interaction with the tumor microenvironment is essential for developing effective cancer therapies.Exosomes are small membrane-bound vesicles that play a critical role in cancer progression, including metastasis and drug resistance. They are produced by various cell types, including tumor cells, and contain a variety of biomolecules such as proteins, lipids, and nucleic acids. Exosomes facilitate intercellular communication by transferring these cargoes to recipient cells, where they can influence cellular behavior. In cancer, exosomes contribute to tumor microenvironment (TME) remodeling, angiogenesis, and epithelial-mesenchymal transition (EMT), which are essential for tumor growth and metastasis. Additionally, exosomes can promote drug resistance by transferring resistance-related molecules to cancer cells, making them more resistant to chemotherapy and other treatments. Exosome biogenesis involves the formation of intraluminal vesicles (ILVs) within multivesicular bodies (MVBs), which are then released into the extracellular space. This process is regulated by various proteins, including the ESCRT machinery, and can be either ESCRT-dependent or ESCRT-independent. Exosomes are composed of a complex mixture of proteins, lipids, and nucleic acids, which reflect the donor cell's characteristics. The lipid composition of exosomes is also cell-specific and plays a role in their biogenesis and function. Tumor-derived exosomes (TDEs) play a significant role in tumor progression by promoting angiogenesis, invasion, and metastasis. They can induce EMT, which enhances the invasive and metastatic potential of cancer cells. TDEs also contribute to therapy resistance by transferring resistance-related molecules to cancer cells, enabling them to survive and proliferate despite treatment. Additionally, TDEs can modulate the tumor microenvironment by influencing immune cells and promoting the formation of a pre-metastatic niche. Exosomes have potential applications in cancer therapy, including targeted drug delivery and immunotherapy. They can be engineered to deliver therapeutic agents such as chemotherapeutic drugs, functional RNAs, and proteins to cancer cells. Exosomes can also be used to modulate the tumor microenvironment and enhance the immune response against cancer. However, challenges remain in the clinical application of exosome-based therapies, including the need for further research to optimize their targeting and therapeutic efficacy. Understanding the mechanisms of exosome biogenesis, function, and interaction with the tumor microenvironment is essential for developing effective cancer therapies.
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