Cells are the basic structural units that are used to build all of the organs in your body. A surface membrane surrounds each cell, just like your skin surrounds you. The cell membrane controls the entry and exit of different things, including food and specific molecules that can change the rate of cell growth and division.
One way that the cell membrane can bring in other molecules is within small bubble-like structures that pinch off and move inside the cell. Such bubbles are called endosomes (inside cell).
Zehui (Lesley) Li, a student at the University of Toledo, is studying chemical messengers between cells and how they can potentially be used to treat cancer.
Once inside the cell, each endosome can make even smaller bubbles within it. These smaller bubbles are called intraluminal vesicles (ILVs). These ILVs are so small that they can only be seen using a very high-powered microscope.
Scientists have now discovered that endosomes can return to the cell surface, where they fuse back with the cell membrane and release small ILV bubbles outside the cell. Once they leave the cell, the tiny bubbles are called exosomes (outside cell).
These exosomes float in your body fluid and eventually attach to other cell membranes and enter the new cell. After they move in, molecules inside of the bubbles will be released into the new cell to affect cell growth and other cell activities.
These tiny exosomes represent an important way for cells to communicate and influence each other, because they often carry signaling molecules and other materiel (good or bad) from their original cell.
However, there is still much we do not understand about these communicating exosomes, such as how their production is controlled, which cells they specifically communicate with, and how many different types of communication they use.
Researches found that cells treated with a unique chemical produced many more exosomes.
UNIVERSITY OF TOLEDO Enlarge
Our research laboratory is very interested in this important method of cell communication specifically between cancer cells. Both normal cells and cancer cells can release exosomes, which can be found in different body fluids, such as blood, urine, and saliva. The liquid medium used to grow cells in culture dishes in the laboratory also contains exosomes released from the growing cells.
There is now a great deal of interest within the scientific community in the molecular content of exosomes released from cancer cells, because they might contain different molecules that send different messages, compared to exosomes released from normal cells. Such information could be used to detect the presence of cancer or to monitor the response of cancer cells to therapy.
An additional exciting investigation is to use these tiny exosomes as carriers for drugs to treat cancer and other diseases. One of the major technical hurdles is how to make cells in culture produce exosomes in large amounts.
Our research laboratory at the University of Toledo College of Medicine and Life Sciences, the former Medical College of Ohio, has been investigating new drugs to treat brain tumors. We became very interested in the exosome investigations after we began studies with a unique chemical, abbreviated MOPIPP. We discovered that MOPIPP causes balloon-like structures, similar to endosomes, within brain tumor cells.
We then wondered whether these endosomal structures could also produce exosomes. To answer this question, we treated human brain tumor cells in culture with MOPIPP and then used specialized methods to analyze exosomes from the liquid medium surrounding the cells.
We found that the exosomes and their contents that we collected from the MOPIPP-treated cells were similar to exosomes collected from untreated cells. But, to our surprise, the cells treated with MOPIPP released three to five times more exosomes than the untreated cells.
Most importantly, the cells treated with MOPIPP continued to grow normally, suggesting that, except for the larger bubbles and increased exosome production, MOPIPP did not have any lasting ill effects on the cells.
We now plan to investigate the exact mechanism that leads to the large boost in exosome production after MOPIPP treatment. These exciting preliminary results indicate that MOPIPP and similar chemicals could be useful as novel tools to produce exosomes in large-scale for cancer therapy.
Zehui (Lesley) Li is a student earning her PhD in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Lesley is doing her research in the laboratory of William Maltese, PhD, in the Department of Cancer Biology. For more information, contact Zehui.Li@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical.
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