Erica Sloan: 'Stress can increase cancer spread'

Erica Sloan recently visited the CNIO (Spanish National Cancer Research Center) as a speaker at the international conference on metastasis organized by CNIO researchers Eva González-Suárez, Héctor Peinado and Manuel Valiente, with the support of La Caixa Foundation.

Why did you take on researching the relationship between the nervous system and cancer?

I started to study metastasis and then moved on to researching how nerves control viruses. While studying HIV, I observed that immune cells located near nerves were more prone to become infected with the virus, which accounted for a worsened disease progression. All this was happening in lymph nodes where cancer also spreads to. So I wondered what would happen if, instead of suffering from a viral infection, a peson suffered from cancer. How would nerves affect tumor cells? That’s how we started studying the effect of neurotransmitters – substances neurons use to communicate with each other – on cancer.

Could you observe any effect?

We found that stress makes cancer spreads more rapidly. That was ten years ago. We then went on to study how stress neurotransmitters make tumor cells more invasive. We found that under stress, blood vessels in the tumor are remodelled. This means that not only does stress make tumor cells more invasive, but it also creates more pathways for tumor cells to escape from the tumour and disseminate through the body.

You study the relationship among stress, cancer and the immune system, that is, the body’s defenses. How do the changes you have just described affect our immune response?

Defensive immune cells respond to stress in a very different way to tumour cells. While tumor cells become more invasive, immune cells do exactly the opposite: they stay still. A healthy immune cell travels around the organism looking for other immune cells, so that they can start a coordinated protective response when they encounter a threat. But, under stress, neurotransmitters cause immune cells to freeze, stopping them from interacting with each other and making them unable to stage a defensive response.

The effect is thus twice as negative.

That’s why I consider stress signaling through the sympathetic nervous system [which is also known and the fight-or-flight response] is so important in cancer. This signaling acts on cells in the tumour and in the immune system, it triggers vascular changes and probably also other effects that are being studied by other groups.

Does this mean that stress increases the risk of cancer?

The term risk implies that it can affect the possibility of getting cancer in the first place. So far we don’t have so much evidence for that. Rather, what we are talking about is that stress increases the progression of cancer once it has already appeared.

But very often the influence of stress is played down.

Yes. We tend to consider stress a weakness, to think of it as something that exists only in our minds. But stress is not only in our mind. Its effects spread out to the whole organism, including the tumour microenvironment. Perhaps that shouldn’t come to us as a surprise, we all feel our heart racing when we face a threat.

Is there a biomarker that could alert us whenever we are experiencing too much stress?

Part of the problem is the lack of an external metric to determine how stressful each stimulus can be. Also different people will respond to the same stimulus in different ways. Therefore, the best biomarker is how stress acts at on our cells, to affect gene expression. For instance, how stress affects genes with a protective role in health or conversely, genes that worsen cancer. Some other groups have identified dozens of genes that are switched off or on following stressful experiences.

You have discovered that a drug already used against hypertension – a beta-blocker – has also an effect against cancer.

Beta-blocker drugs reduced the effect of stress on the cardiovascular system. They muffle the stress response and stabilize the heart. We have carried out several studies with breast cancer patients. In one of them we followed up patients for years and found that in patients taking the beta-blocker carvedilol, cancer didn’t spread as much and they experienced a longer survival. These findings suggest that we need to explore more deeply the use of carvedilol to slow down cancer progression. This drug is already used in oncology to alleviate the side effects of chemotherapy.

Coming back to stress, it is difficult not to feel it when faced with a cancer diagnosis. How can we avoid it?

Having cancer is very stressful, there’s no doubt about it. Our challenge is whether we can treat the patient as a whole, not only their cancer. Because stress also affects many aspects of our health, perhaps this is a challenge not only for the patient with cancer, but for the whole health care system.

Image: Erica Sloan / Mónica G. Salomone CNIO.