The widowhood effect accelerates cancers

Sociologists and psychologists will tell you that “life events” - like the loss of a lifelong partner - are associated with an increased risk in the aftermath of conditions like cancer for the survivor. But is this actually caused by the broken bond, or is it that the two shared risk factors and so it’s actually inevitable? Now, as he explains to Chris Smith, an intriguing set of experiments carried out by the University of South Carolina’s Hippokratis Kiaris confirms that something in the bloodstream of a bereaved survivor promotes the growth of cancers…

Hippokratis - It is designated actually as the widowhood effect, or the broken heart syndrome. And it is more prominent during the first few months after we lose a partner and the risk decreases after that.

Chris - How do you know, though, that birds of a feather don't flock together with a situation like this, whereby, you know, I've married my wife; we're of similar social class, similar education, similar background, similar lifestyle. So, therefore, the kinds of things that happened to me are likely to happen to her, at roughly at the same rate, give or take; how do we dissect away those confounders from this?

Hippokratis - This is a very important question and brings up the question of homogamy - the likelihood to marry individuals of similar health. These are the questions we wanted to address, because all these epidemiological studies, no matter how well they are being designed and controlled, they always have caveats. By remaining alone, one changes his or her diet, acquires or abolishes habits, all of which may have health impacts. So, we need to dissociate these effects and really explore if there is a biological basis to the widowhood effect.

Chris - Difficult to study though, isn't it, because humans aren't unique, but they're quite rare in terms of how long we live. And the fact we do form these long-term relationships with a single partner, and then do feel enormous grief when we lose that partner. How can you test that biologically?

Hippokratis - So this is the reason we turn to the deer mice - animals of the genus Paramyscus. These are monogamous. They establish long-term pair bonds based on matings, and they are ideal for our studies. So we did a few different experiments. We took these animals that have either established these pair bonds, or animals that these pair bonds were disrupted because the males had been separated from their female partners. Then we implanted these animals with cancer cells in order to develop tumours. When we took these tumours, we transplanted them into conventional laboratory mice, we recorded striking differences. Tumour growth was recorded predominately in mice that received tumours from the bond disrupted animals, but not from the bonded animals.

Chris - This would suggest, then, there is something in the biochemical milieu of a pair bond-disrupted mouse that in some way, re-patterns, the growth potential of pathological tissue, like a tumour. Can you recreate that in the dish though? Do you need a mouse to do that? Could you take out, for example, the serum - the plasma - that's in that animal, that's had its bond disrupted and grow tumours in the dish with that serum and recreate the effect that way?

Hippokratis - This is exactly what we did next! So we took serum from animals that were either bonded or bond-disrupted - separated - and we added cancer cells under conditions that the cancer cells form the so-called "organoids" or tumours spheroids. And we saw lung cancer cells that formed in the presence of the serum from bonded animals did not grow much as compared to the cancer cells that grew in the presence of serum from bond-disrupted, separated animals, that grew a lot.

Chris - Did you do the experiment where you took the serum from an animal before it bonded, then the serum from the same animal after it bonded and then serum from the same animal after that bond was disrupted and repeat the experiments across all three, to see if there was genuinely an effect and it wasn't just that animal. There was something about disrupting the bond in that animal that made the organoids grow differently?

Hippokratis - This is a very important experiment. We did actually such experiments. We really show these differences.

Chris - Putting all this together, then. It strongly suggests that, in response to pair bond disruption, something ends up going around in the bloodstream that has a pretty profound effect on the way cells that have the potential to be pathological, like cancer cells, will grow, but not just in the short-term while they're exposed, it must reprogram the growth potential of those cells or select for cells that are nastier inherently. So have you got any insights from this yet as to what those factors might be?

Hippokratis - Yes. This is actually a very important question, and it is on-going research we are currently performing in the lab. It is rather likely that certain hormones are associated with these effects and their activity should change in relation to both our bonding experience and status as well as to the stress that is induced when the bonds are broken. Such hormones, for example, can be oxytocin, can vasopressin. Both of these are hormones associated with bonding, as well as cortisol, for example, which is associated with the stress responses and all of these hormones and others that I didn't mention now are either directly or indirectly been linked to cancer and other pathologies before.

Chris - Would one logical kind of conclusion from this be that you need to investigate whether or not giving certain drugs even antidepressants, for example, or other agents acutely around the time that the pair bond is broken, would that be protective? And are you going to do those experiments to see if you can, you can stop this effect?

Hippokratis - Yes, it is possible for such drugs to function like that. And it is really in our interest to start exploring the effects of these drugs, that we know that they change our mood and, uh, mitigate in a way, the consequences of loneliness and start exploring whether they have real effect in our physiology acting directly on tissues and protecting us from disease.