Unraveling cancer exosome release by using a reporter protein

PhD student Medical Chemistry Maarten Bebelman and Michiel Pegtel (VUmc) discovered new pathways in cancer cell physiology; knowledge that can help to develop novel strategies for targeting exosomal communication in cancer.

01/25/2018 | 1:30 PM

Cells communicate with each other by releasing and taking up small packages of cellular material, referred to as exosomes. These extracellular vesicles have many important functions in healthy individuals, for example by aiding the immune system or maintenance of neurons in the brain. Unfortunately, exosomal communication is deregulated in many diseases including cancer, where exosomes from cancer cells promote tumor growth and metastasis.

Although the role of exosomes in cancer becomes increasingly clear, our knowledge of the cellular mechanisms that mediate and control cancer exosome release is limited. One of the reasons for this is the small size of exosomes (± 100 nm), which makes it difficult to detect their secretion using normal light microscopy. To overcome this problem, researchers from the group of Michiel Pegtel (VUmc Cancer Center Amsterdam) developed a reporter protein that gives bright flashes of fluorescence every time a cell releases exosomes. This allowed the researchers to follow exosome secretion in real-time in single cancer cells.

Using this system, Maarten Bebelman, PhD student in the groups of Martine Smit (Medicinal chemistry, VU) and Michiel Pegtel, discovered that exosome release can be triggered by the activation of signaling proteins, so-called G protein-coupled receptors, in the cell membrane. Furthermore, the researchers identified several key proteins that contribute to the secretion of exosomes from cancer cells. Future studies using this reporter protein will help to increase our understanding of exosome physiology and to develop novel strategies for targeting exosomal communication in cancer.

The researchers published their findings in the Journal of Cell Biology.

Figure: Projection of exosome release events (yellow spots) in a cervical cancer cell (blue) over a time-course of 3 minutes