Oct 30, 2014

Interviewer: New insights into how cancer cells gain the deadly power to grow uncontrollably up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Jared Rutter Professor at The University of Utah. Dr. Rutter you've published a report, "Molecular Cell," describing what could be a key change that takes place in cancer cells that gives them an advantage over the normal cells in the body. I think what's fascinating about your discovery is that it relates to a hypothesis that was posed early last century. First of all, can you explain what this hypothesis is, The Warburg Effect?

Dr. Rutter: Dr. Warburg discovered that cancer cells do a different kind of metabolism than normal cells. That fundamental observation has been born out repeatedly in the years since and now has become a very active area of research both in discovery based research and academia, as well as more applied research going on in companies trying to treat cancer. The question will be whether that can now be exploited and in treatment.

Interviewer: You can tell me if I have this right, in a normal cell sugars or carbohydrates eventually go down a pathway where the cells powerhouse, mitochondria, makes energy, but in cancer cells it's different. What happens in cancer cells?

Dr. Rutter: So cancer cells go through about half of that pathway. They take the carbohydrates about halfway through that pathway but they don't take the carbohydrate into the mitochondria, the powerhouse of the cell, they do other things with it, and specifically they use that carbohydrate to create the building blocks that will enable them to make a new cell. So obviously cancer is a disease of overgrowth of cells dividing and duplicating themselves more rapidly than they should and that's what creates a tumor, or what creates the cancer.

Interviewer: I think your work really argues that there's a protein called MPC1 that is a key component of this shift in metabolism. What is MPC1?

Dr. Rutter: The MPC1 and MPC2 together make up a protein complex that enables carbohydrates in the form of a specific molecule called pyruvate to enter the mitochondria, again the powerhouse of the cell, and enable the mitochondria to then take that pyruvate and use it to create energy.

Interviewer: And what happens to this protein in cancer cells?

Dr. Rutter: We've shown that in a large number of cancers, most prevalently in ovarian cancer, that the part of the genome that encodes this protein is just lost. It's lost from the genome and therefore the gene is not expressed, the protein isn't made, and this MPC protein complex is just never formed. So what we did next was pretty simple in that is the hypothesis is that it being lost is actually important then what if we put it back in and force the cancer cells to make this protein, and what happens is they lose their ability to behave like cancer cells. Their metabolism reverts from the way that most cancer cells do in metabolism to be a much more normal type of metabolism and they lose the ability to form tumors in different situations, and so...

Interviewer: Wow, that's amazing.

Dr. Rutter: Yeah.

Interviewer: So you saw that effect both in a dish but also in the context of an animal too, correct?

Dr. Rutter: That's right. So yeah exactly, we saw it in a dish and then the gold standard for this type of experiment is to put tumor cells, cancer cells, into a mouse and ask whether they can form tumors, and what we found is that the cells that had this protein, this MPC protein, put back in were quite dramatically impaired in their ability to form tumors in mice and how fast those tumors grew.

Interviewer: What kind of difference are we talking about? I mean is it there's a tumor compared to no tumor, or is it a difference in size, or is it the number of tumors that form, or...?

Dr. Rutter: Yeah that's a good question. I would say the way that the experiment was done it really wasn't done in such a way that we could see a tumor versus no tumor. So what was done is to inject about 100,000 cells into the flank of a mouse and then so that you already have a fairly large number of cells there and then look at the ability of those cells to grow, form a tumor and how big that tumor becomes, but always they grew slower when this MPC protein was put back in.

Interviewer: When you're talking about the progression of cancer where do you think metabolism fits in the scheme of things? Do you think it might be one of the early changes that must take place in order for a cell to become invasive for example or...?

Dr. Rutter: Yeah we do, we actually know that. In some cases that there are certainly many cancers where one of the early steps is to manipulate the metabolic profile of those cells.

Interviewer: And what are you most excited about going forward?

Dr. Rutter: Well I think there are a few different things that I would say we're most excited about. I would say first is just trying to understand what is the cause of the failure of the cancer phenomenon when we force cancer cells to make that protein. We just really don't understand it and whatever the answer is it will be interesting, and then the second, like we've talked about, is to try and understand how to exploit this observation to make a difference in the context of the treatment or diagnosis of cancer, and we have some ideas that I think are quite good as to how to try and translate that into direct clinical application.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

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