Evolution of exosomes – From cellular garbage trucks to special delivery couriers

by Jill Russel, PhD

When scientists first identified exosomes – lipid vesicles ejected by cells – they were thought to serve as tiny garbage haulers, filled with unneeded cellular junk.

Decades of research have shown exosomes instead to be engaged in communication among cells to influence a variety of ends. An invited review of the field by MD Anderson researchers published this month in Science captures the remarkable breadth of activity and biomedical potential of these extracellular vesicles.

“This is an exciting field because exosomes are found in all biological fluids and are secreted by all cells. Understanding exosomes’ function and biology could lead to novel diagnostic and therapeutic strategies for many different diseases,” says review co-author Raghu Kalluri, M.D., Ph.D., chair of Cancer Biology and director of the Metastasis Research Center. Kalluri leads a laboratory of 20 scientists who focus on biology and function of exosomes.

Exosomes play role in cancer, other diseases

Exosomes were discovered 30 years ago, but the recent explosion in exosome research has been driven by advances in technology that allow the virus-sized particles (approximately 40 to 160 nanometers in diameter) to be detected and isolated.

Exosomes are extracellular vesicles formed through double invagination of the cell membrane. Think of them as microscopic semi-trucks that carry cargo to cells. This cargo can include a mix of membrane proteins, cystolic and nuclear proteins, extracellular matrix proteins, metabolites, messenger RNA, noncoding RNA species, and DNA. The cargo exosomes carry depends upon their cells of origin, the cellular microenvironment, and the size of the exosome.

Exosomes form an intercellular communication network that can alter the biological response of recipient cells (for example, inducing cell survival, apoptosis, or immunomodulation) depending in part on the exosomal cargo.

Studies covered in the review article suggest that exosomes could play roles in:

• reproduction and development (e.g., promoting sperm maturation, inhibiting HIV-1 infection in sperm, preventing infection in the placenta, and promoting postnatal health and growth via breast milk)
•  adaptive and innate immune responses to cancer and to infectious agents
• metabolic diseases and cardiovascular fitness
• neurodegeneration (e.g., promoting or limiting the accumulation of unfolded or misfolded proteins in the brain)
• cancer (e.g., influencing neoplasia, tumor growth, metastasis, paraneoplastic syndromes, and resistance to therapy)

Exosomes also might serve as a “Trojan horse” for viruses to infiltrate cells and can pass easily through the blood-brain barrier.