Building tumours in the lab
Cancer causes tumours, but tumours aren't just made out of cancer cells, as Kat Arney found out when she went to visit Fran Balkwill, Professor of Cancer Biology at Barts Cancer Institute, Queen Mary University of London, who is working on ovarian cancer, which spreads inside the body, particularly into the peritoneum - that’s the lining inside the abdomen - and the omentum, the scientific word for tummy fat.
Fran - My interest is the entire cancer. A lot of people think that cancers are born of malignant cells that have gone out of control. And this is true but that’s only half the story. When we think of really, probably all cancers, then they are actually a mix of the malignant cells, the cancerous cells, but a whole host of other cells that the cancer has recruited and, in some ways, corrupted to help the cancer grow and spread. 50% or more of any lump that is a cancer can be these normal cells that are promoting the cancer growth and spread.
Kat - What type of cancer are you looking at?
Fran - We’re looking at a type of ovarian cancer called high grade serous ovarian cancer. What you find when you look is that you find a mixture of fat cells, which are in parts of the peritoneum, and we think the cancer can use that fat to help them grow. Then you find fibroblast builder cells, you find new blood vessels, you find lot’s and lot's of immune cells that really should, and we know they could, fight the tumour but they don’t, and the malignant cells as well. There’s up to 20 or more different cell types actually in a cancer alongside the cancerous cells.
Kat - But certainly from my experience of working in a lab, you just look at cancer cells growing in a plastic dish but, obviously, that doesn’t capture all this diversity you’re talking about?
Fran - No. Absolutely and that’s the problem. Now that’s why we use mouse models of cancer because then you can in a living organism, but sometimes we need to have all human cells. Some of the new treatments actually have antibodies that act against human cells and not mouse and so we really need to compliment the mouse models, we need to have some human models. So how do we set about this?
Kat - The human lab…
Fran - Yeah. The human lab. We are not made of plastic and cancers are more than just cancer cells growing on a plastic plate. But with all the advances in bioengineering and regenerative medicine we think, and many people are trying to do this now, that we can begin to build complex three dimensional models of more than one cell type. More than just a cancer cell and answer some of these basic questions about how tumours form as well as what new treatments we can use.
Kat - How do you go about doing that then? How do you about reconstructing all this three dimensional glory of a tumour in the lab?
Fran - It’s with great difficulty I think I would say. But the approach that we’ve taken is to first deconstruct, so we get from surgery the omentum, which is part of the peritoneum from patients with high grade serous ovarian cancer.
First we found out many things, not all of them, but many things that we thought would be useful so that we would have a kind of template for a model, but also we would be able to validate. We would be able to say how close is any model we build to the real thing. So we did that for quite a long while and that’s proved extremely useful and also rather interesting. We learnt things about the tumours that we didn’t know before when we were just looking at the cancer cells.
Now we’ve taken various approaches; the most promising is to build an artificial omentum because in normal people the omentum is mainly fat cells. So we’ve been able to grow an artificial omentum and we have some idea how stiff it should be from the deconstruction and we have some idea about what other cells are there. Then we are growing the tumour cells, and the fibroblast builder cells, and also some other cells called mesothelial cells and we’re trying to recreate a model where the tumour is first invading that omentum. And also another model where the tumour is already there in situ with all the cell types.
We haven’t got all the cell types yet and the next challenge is the immune cells. But we’ve got some of the major cell types and all from the patient putting together and now we’re just testing to see how close those cell types resemble, in some of their functions and things that they make and things they do, the tumours that we take from the patients.
Kat - So it’s a bit like taking a house and unbuilding it brick by brick, taking everything apart, the beams. the bricks, the insulation, looking at what you’ve got and then trying to reconstruct that again?
Fran - Yeah. I think that’s not a bad analogy. It’s very complicated. We’re never going to be able to completely recreate the cancer obviously. The important thing now is to find questions that we cannot answer in any other way, or we need to complement our studies in the mouse models and then work out what combination of cells we think can answer those questions.
Kat - So now you’re managing to grow these little tumours, these little systems in the lab, what’s the ultimate goal? What are you going to do with them?
Fran - First we need to check that they do enough to resemble the human tumour and then, from our point of view, we want to find new treatments that disrupt the interaction between the malignant cells and all those cells that they corrupt and recruit because, if we can do that, we can break of some of the supply lines of the tumour. We also want to use them to understand how the tumour cells and the other cells interact to form tumours in the first place. So it’s understanding some basic cancer biology, but also a complementary way to the other ways we have of testing new treatments.
Kat - I look at some of the stories that are coming out of world of tissue engineering, and researchers using things like 3D printers to think about making new organs and all this kind of stuff. What would be your dream for making these kind of tumours in the lab?
Fran - Well, I think that you’re absolutely right, and we’ve just got some funding to get a 3D bioprinter. It’s going to take us a while; it’s not going to happen overnight but I think it’s a nice idea. I was talking about this to a load of clinicians the other day, oncologists. One came up to me afterwards and said “do you know when you were talking about that, I had a vision of a bioprinter printing little tiny living people.”
Kat - That would be the ultimate model, wouldn’t it?
Fran - Yes. Unfortunately there’s something about the size of cells that make us the size we are and, unfortunately, you can’t make tiny people but it’s just a wonderful idea.