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CancerA run a day keeps the tumour at bay

Exercise
protects against cancer. Researchers now understand why

Print edition |
Science and technology
Feb
27th 2016

AMPLE evidence shows that
exercising regularly reduces the risk of cancer. Similarly, those who have
survived the disease are less likely to see it return if they engage in lots of
physical activity after treatment. All this suggests that such activity triggers
a reaction in the body which somehow thwarts cancer cells, but the details of
the process have remained murky. Now, a team led by Pernille Hojman at
Copenhagen University Hospital, in Denmark, has reported in Cell
Metabolism that the key to the mystery is
adrenalin.

Dr Hojman began her work by verifying that exercise truly
does have beneficial anti-tumour effects. She and her colleagues gave some of
the mice in their laboratory activity wheels, which the animals could run around
inside as much as they liked. Other mice, meanwhile, were given no opportunity
to exercise beyond moving about inside their cages. The researchers then induced
mice of both sorts to develop one of three types of cancer. Some, they injected
with a substance called diethylnitrosamine, which causes liver cancer. Others,
they injected below the skin with melanoma cells, which then set up shop where
they had been injected. Others still had their tails inoculated with melanoma
cells. In mice, previous experience has shown, this leads to melanomas forming
in the lungs.

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The results were instructive. While all mice injected
under the skin with melanoma cells developed that cancer, the tumours in animals
which had had access to a running wheel were 61% smaller after six weeks than
were those in mice that had been unable to exercise. A similar reduction in size
(58%) pertained to lung tumours. And, of the mice injected with
diethylnitrosamine, only 31% of those with wheels in their enclosures developed
tumours at all—in contrast to a 75% tumour-development rate in mice lacking
access to a wheel.

To try to understand why exercise does this, Dr Hojman and
her team put under a microscope some of the tumours they had induced. They found
that those from well-exercised mice contained more immune cells than equivalent
tumours from inactive animals. Specifically, the former had double the number of
cytotoxic T-cells, which kill off body cells that are damaged, malfunctioning or
infected with viruses. They also had five times more natural killer cells, a
type that sounds the alarm and attracts other immune cells.

In light of these discoveries Dr Hojman repeated the
experiment, this time on mice that had been engineered to lack cytotoxic
T-cells. Again, she found that mice with access to wheels had smaller tumours.
This suggested that the natural killer cells, not the T-cells, were the
responsible agents. A third experiment confirmed this. She sabotaged natural
killer cells by giving mice an antibody that eliminated these cells while
leaving the rest of the immune system intact. With the natural killer cells
gone, the tumours of all the mice, regardless of whether or not they could run
in a wheel, grew to the same size.

Dr Hojman knew from past work that epinephrine, a hormone
also commonly known as adrenalin, has the potential to mobilise natural killer
cells. She knew, too, that this hormone’s levels in the blood rise during
periods of physical exertion. That led her to wonder if it is epinephrine which
is behind the cancer-thwarting effects of exercise.

To find out, she ran a fourth experiment, in which mice
induced to have cancer were injected either with epinephrine or with saline. The
hormone performed well, reducing the growth of tumours by 61% in mice that had
no access to a wheel. However, this was not as impressive as the reduction of
74% which the team saw in control mice that got regular exercise. There was,
they concluded, something else involved. And they found it in the form of
interleukin-6.

Levels of this molecule also spike during exercise—and it,
too, helps immune cells home in on tumours. When Dr Hojman and her colleagues
exposed sedentary mice both to epinephrine and to interleukin-6, the rodents’
immune systems attacked the tumours in their bodies as effectively as if those
animals had engaged in regular wheel-runs.

Dr Hojman’s findings, then, suggest that epinephrine and
interleukin-6 could be used as anti-tumour drugs. She is not proposing that they
should be a substitute for exercise in those who are merely lazy—not least
because exercise brings benefits beyond curbing oncogenesis. But people who are
too old or too ill to be active might thus gain exercise’s anticancer benefits
without the need to get sweaty.

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