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Researchers at the University of Nebraska-Lincoln's Department of Biochemistry found a way to stop immune-suppressing cells from feeding off lipids, or fatty acids. Concetta DiRusso and Paul Black, along with a team of collaborators, found in doing this, cancerous tumor growth was slowed in mice. Now the hope is to test this in humans.
Brandon McDermott, NET News: Concetta you were able to block out, with this research, an energy source for cancer cells in cancer patients, can you tell us more about that?
Paul Black (left) and Concetta DiRusso (right) co-authored the study. (Photo Courtesy Craig Chandler)
DiRusso: Cancer is made up of multiple tissues, and they're rapidly growing cells and it's a rapidly growing mass, if you will. To feed that growth, you require fat -- as an energy source, but also as a source of essential fatty acids -- in order to allow that to grow. So by blocking that, with a small compound that might become a drug, we're able to limit the growth of the cancer, and its progression to metastasis.
McDermott: Paul, I've heard you compare this to a gate sitting on a membrane that controls the amount of fat that gets in. Can you elaborate on that gate simile?
Black: The idea behind the protein is that one region of the cell that sits on is the plasma membrane. The plasma membrane, essentially delineates the outside of a cell to the inside of the cell. So, nutrients, including fat, have got to be able to move across that membrane in a highly regulated manner. They just don't get across in a happenstance way.
This particular protein, fatty acid transport protein, actually sits at the membrane and functions to regulate the amount of fat that actually enters into the cell. Now, it's not the only one that does that, there are other ones, but this is one of the major proteins that actually does this. Once the fat gets into the cell, then it is destined to go into downstream metabolism.
So, in the context of normal cell growth, there's going to be a certain amount of fat that comes in the cells, tend to be opportunistic, they don't want to make fat — they can utilize it. So the gate's now going to be more open, if you will, there's more of the protein to drive the fat in.
A look at the cell membrane, protein and lipids. (stock photo)
You get more fat in you can now move that fat into metabolism, and in so doing, you can then increase the amount of metabolic fuel in order to power metastasis or cell growth.
McDermott: Concetta, this research didn't necessarily start with targeting cancer. Can you tell us where it started? And could this also go beyond cancer to help fight other diseases?
DiRusso: So actually, when we started out, we were targeting what are called lifestyle metabolic diseases. So the one people know the most about is type two diabetes or insulin resistant diabetes, that occurs very frequently as we age. With that type of diabetes, we aren't targeting fat into adipose tissue or fat tissue where it really belongs. But we're, we're only more slowly acquiring it, so you wind up more in the bloodstream with more fat in the bloodstream.
This then can be taken up by tissues where you don't want to store fat. So a major one is liver, and you wind up with something called non-alcoholic fatty liver disease. Another is if you talk if it goes into the pancreas, it could help it could prevent insulin synthesis and secretion. It can wind up in the heart where it might cause heart failure. So we were targeting absorption across the intestine, and then absorption and distribution into fat specifically, we wanted to make sure that that was the target tissue.
McDermott: This is not necessarily an end all for eradicating all tonight, but is it a piece of the puzzle? Will it help you know where to go next with research?
The research included help from the Wistar Institute's Dmitry Gabrilovich lab. (Stock photo)
DiRusso: Oh, yes, very definitely. This particular protein we noted very early on is highly expressed in tumors. And it turns out, in fact, that when this is elevated as in the immune cells that we're targeting in this collaborative work, it winds up helping to restrict the tumor growth.
McDermott: Paul, I've heard you say about collaboration that “the old days of researchers siloed themselves off in their own work is over.” How has research and collaboration changed overall, and for the both of you?
Black: History changed dramatically. You're always on a learning curve. But your learning curve can only go so fast. You have got to rely on your collaborators to bring in that key expertise. The key expertise in this particular study, as Concetta mentioned with a Gabrilovich lab, is that they're really good at cancer biology -- they're really good at understanding the immune system and the interrelationship between the immune system and cancer progression.
We didn't have that expertise, but we had the expertise of understanding the mechanism of how this protein works. Concetta’s lab had the expertise of identifying the small molecule inhibitors that blocked the progression of these tumors because it blocked the uptake of the fat.