Cancer, wounds and inflammation – something fishy going on

The parallels between cancer and wound healing have been the subject of Professor Paul Martin’s academic attention for some time. 

And after he was diagnosed with Hodgkin lymphoma a year ago, they received his personal attention too. One Friday afternoon over tea and cake, Professor Martin told us about his cancer journey and how it’s affected his research.

The wound that does not heal

When you cut yourself, immune cells rush to the wound to clear any germs that might cause infection. Not only that, but they nurture surrounding cells to help the wound heal.

But what about cancer, sometimes referred to as “the wound that does not heal”?

Because it’s been known for some time that immune cells also seek out cancer cells, Professor Martin wanted to see if the immune cells recruited to cancers behave like they do in regular wounds. And he wanted to find out if the immune cells nurture the cancer cells, and help them grow.

To help answer that question he turned to a seemingly strange choice of animal – the zebrafish, a small, transparent fish.

By adding a human cancer-causing gene to zebrafish cells and also making those cells glow under ultraviolet light, Professor Martin can see cells in the fish that are the precursors of cancer. And because the fish are see-through when they’re young, he can watch what happens to them when immune cells seek them out, using a fluorescence microscope.

An adult zebrafish

Professor Martin told us: “Our presumption was that the glowing cancer cells would grow a bit to become a lump that would disturb the normal tissue around them, and only then would they trigger the immune response. But that’s not the case.”

“The immune cells, called neutrophils and macrophages, generally find that ‘wannabe’ cancer cell before it’s even had a chance to divide. And once they’ve found it, the cancer cell starts dividing rapidly. So the immune cells are being drawn in and supply the cancer cells with something to help them grow.”

“We’ve now found out that the thing they’re supplying the cancer cells with are molecules called prostaglandins, which are growth promoting factors.”

Professor Martin and his team gave the fish drugs that specifically block the enzymes that make prostaglandins. It turns out those drugs can stop the fish cancers growing.

The team can also stop the fish cancer in its tracks by making the fish completely free of immune cells, the vehicles that are delivering the growth-promoting prostaglandins. And if they then add prostaglandins back to the water the fish swim in, the cancer cells will start growing again.

You can hear Professor Martin talk about his fish studies in his recent TED talk. Research will be the key to finding out if the results from the fish experiments also hold true in patients – like Professor Martin himself.

Professor Martin’s cancer journey

Let’s take a step back, to before Professor Martin found out he had cancer. The journey began, funnily enough, on a fishing trip. But not one based in his lab.

Professor Martin’s biggest ever catch, an impressive 7lb bass.

“Being a scientist can be stressful, so I have hobbies. I go sea fishing, and there a big gaps where nothing happens. On one such occasion I was rubbing my neck and I found a lump, which I thought was just a salivary gland with a pip stuck in it.

“I was also experiencing night sweats, but I just thought I was going through the male version of the menopause or something. But actually those are a key characteristic of lymphoma.”

And after some persuading by a young surgeon in his lab he got his lump checked out. He had a biopsy, after which he was diagnosed with Hodgkin lymphoma.

“Quite frankly I was terrified. But very quickly I had the surgery and was on chemo before I knew it. I thought chemo was pretty much a doddle the first round or two. I even kept going to my kung fu class. But by round four I was worse than fragile.

“Because my job is so physically easy – I just sit in my office and boss my team around – I could keep going to work. And those things, being able to work and the kung fu – they help keep you going.”

“The biggest hit was to my wife and youngest daughter. When the chemo was over and I had my first PET scan I lied to my daughter and said ‘it’s all completely gone, I’m sorted. I’m cured’ – because I knew she was asked by the other kids at school – ‘is your Dad going to die?’ and suchlike.

“But it wasn’t gone. I did have another PET scan a few months later and they couldn’t find any cancer then. Chemo is meant to knacker you out for maybe six months after it’s finished, but I feel fine now after four or five months. Although I do play on it a little bit at kung fu and say I’m not absolutely fit, but I am.” [Editor’s note: Sorry Paul – I think this blog post might reveal your little secret. But go easy on him, guys.]

Game changing

Professor Martin’s journey through cancer has left more than the physical scar of the surgery on his neck. He notices that many things have changed, in both his academic work and his personal life.

“My eldest daughter, she’s 17 and her passion is rowing; she hopes to row for GB one day, and I’m thinking – ‘God, I hope I live long enough to watch her in the Olympics’. It makes you think about things like that, and it’s influenced the type of experiments I want to do now.”

Professor Martin and his lab team on a trip to Cornwall

Professor Martin now has another student looking at how long it takes for immune cells to become involved in tumours following radiotherapy. He said “I don’t think my lab would have done that experiment if I hadn’t been told I might need radiotherapy, although I didn’t have it in the end.”

“I think my lab team were heavily affected by me having cancer. But the thing that affects me most is that I’m chuffed I’m still alive and I get to keep doing this research that I love.”

Sarah

The zebrafish image courtesy of Wikimedia Commons 

With thanks to Professor Martin for his warmth, charm and for sharing his story with us and providing all the other photos in this post.