Exercise stops cancer growing
Can exercise cut cancer risk? Various lines of evidence suggest that it can, but how? Randall Johnson has found that the same stuff that makes your muscles burn when you run also stimulates classes of immune cells that can suppress the growth of cancers. Chris Smith spoke with Randall to ask, could the two be connected?
Randall - A number of studies over the years have found that there are links between increased exercise and physical fitness and decreased susceptibility to cancer. And there are animal model links that have shown over the years that you can induce animals to exercise, mice in particular, love to exercise. They love to run on wheels and do it voluntarily, and that they will get fewer tumours and the tumours will grow more slowly.
Chris - Of course, one possible criticism is that individuals who are more prone to cancer are just lazier.
Randall - Yeah. And their lifestyles may be more prone to induce a malignancy as well. And it's one of the things that you do these experiments to try and test.
Chris - And did you get a sort of handle on that?
Randall - What we did is essentially first started out to just, in our own systems, try and determine whether we saw a decrease in tumour growth when animals were allowed to exercise. And these were in all cases, animals who just had a free wheel put inside their cages. And they were just allowed to run as much as they want. And mice will run up to six, seven kilometers a night. And so we found that animals who got a wheel in their cage that was locked, so they couldn't run, had a greater tumour growth than animals who were actually allowed to run every night.
Chris - Is this a dose-dependent relationship? Because that's one of the other key criteria with cancer causation, isn't it, is it dose-dependent? So if you allow a mouse to run six kilometers, does it get more therapeutic suppression of its cancer than if you restrict it and it's only allowed to do three kilometers?
Randall - Yes. In our study, there were a group of mice that ran much longer than another group of mice. And we segregated them by rough categories, ones that ran around approximately three kilometers a night and ones that ran around six kilometers a night. And we did find a dose relationship in that regard. However, we're now doing experiments where we're much more closely controlling the amount that the mice run, to try and approach that, that very question.
Chris - And putting some numbers on it, how much of a difference did it make to say the volume of tumour in a mouse that exercised versus one that wasn't able to exercise?
Randall - Yeah. We were seeing reductions in tumour growth of quite substantial ones, you know, up to 50%. But of course their cancers weren't being cured. What we seem to see is a link to the role of a specific type of immune cell, the cytotoxic or killer T cell, which in many regards is considered to be a very important controlling element in the immune system to combat cancer. And those cells seem to be much more prevalent in the tumours of animals that exercise
Chris - Your hypothesis being then that exercise in some way, mobilises a particular population of white blood cells, these cytotoxic T cells that will take down tumours and that because there's more of them, the tumour bulk is lower and the animals live longer compared with the ones that don't exercise.
Randall - I need to be careful. There's not more of them in the animal, but there are more attacking the tumour. So we seem to be potentiating their effect on the tumour. We saw that sort of correlation but we wanted to test it. So we did an experiment, you just simply kill off all the animal's cytotoxic T cells. Then the exercise mediated effect goes away.
Chris - Which points the finger strongly at those cells as being a key part of the process. What about doing the opposite? Where if you collect those T cells and put them into an animal that's not allowed to exercise. So it's a lazy mouse. Does it inherit the protection as though it were exercising by doing that?
Randall - Yes. You hit the nail on the head. That's exactly what we did next. We basically took T cells from trained animals and put them into non-trained animals, to coin a phrase. Could we train the T cells? Would they then be better at reducing tumour growth? And in fact, they were
Chris - That's extraordinary. Does this argue then that there is something specific coming out of muscles when they move, when we exercise, that causes these cells to increase their activity? Do we understand, or do you understand yet what is actually driving the link between physical activity and these T cells that seem to have this anti-cancer or cancer-suppressing activity?
Randall - We think we have a good handle on it. One of the really exciting things we followed up on was the muscle produces lactic acid, which we know is important. You feel that in your muscles when you exercise, and that that lactic acid in the blood could actually have striking effects on T cells - improve their performance in combating tumours.
Chris - And have you actually tested that? Can you stimulate T cells with lactic acid and demonstrate they go into this more enhanced weaponised anticancer mode?
Randall - We could. We injected the animals on a daily basis with a quite substantial dose of lactic acid, but enough that we actually were essentially mimicking what would happen from a big bout of exercise. And we saw that when we did that, the high doses actually did reduce tumour growth.
Chris - And so do you think that there might be a solution for people who are couch potatoes? I mean, I'm the worst of them, whereby I can have my cake and eat it quite literally and keep my cancer low by either dosing myself with something that will fool my immune system into thinking I've been a lot fitter and less fat than I am, or stealing someone else's T cells and infusing those?
Randall - There's that! There's always this sort of Count Dracula mechanisms of eternal youth that are out there. And there are cancer therapies that involve reinfusing T cells. And what we hope is that this may help us find ways to treat those T cells to make them better anti-cancer agents when they're put back into patients. I would say, this is pure speculation, of course, there's a lot of lactate in yoghurt. I'm sure you're aware there are these populations in Greece and in the Urals that, you know, the centenarians are a very large proportion of the populations and at least the yoghurt ads they always say it's because of their yoghurt consumption. So it's probably not bad for you to eat more yoghurt.