Turning cancer cells into fat cells

A new approach to halting cancer has been announced this week by scientists in Switzerland. They have found a way to make cancer cells convert themselves into harmless fat cells. The technique relies on the fact that the more aggressive tumour cells - which are the ones actually capable of doing the most damage and spreading to other parts of the body - are also the most chemically impressionable; so it's possible to use two existing, licensed drugs to persuade them to transform from relatively unspecialised cancer cells into inert fat cells that can't grow any more. Chris Smith spoke to Gerhard Christofori, from the University of Basel…

Gerhard - So these cells, the aggressive cancer cells differ from the original tumour cells. And being able to survive the bloodstream, to survive in distant organs and also to become resistant to chemotherapy for example but that also makes them also very plastic. These cells have a lot of potential to convert into other cell types and this is essentially what we tried to use.

Chris - So you're talking about persuading these cells because they're highly impressionable and that's why they're so successful on the one hand, but persuade them to become something a lot less nasty.

Gerhard - Yes. And there we started out to essentially culture these cells in dishes and then we used known factors and treatments that we know from, for example, embryonic development that would make up fat cells for example. So the goal was to convert aggressive breast cancer cells into fat cells.

Chris - And why did you pick on fat cells why do you want to make them into fat bearing cells.

Gerhard - Yes there are two advantages of fat cells. The first is that once a fat cell has formed it's not dividing anymore. It's not producing more cells. The other advantage is fat cells are also highly differentiated so they are kind of in the end stage of the function and they are not returning back to the original cell type. So they would not go back to become an aggressive cancer cell anymore.

Chris - So you did these studies, first of all, in a dish. That was the testing that enabled you to find “what signals do I need to expose these cells to push them into that terminal dead end where they become fat cells and there is no going back.”

Gerhard - Exactly, and then by knowing these signals we could deduce which drugs that are available already could be used to replace these signals and these factors and then use these drugs in a mouse model of breast cancer for example.

Chris - And does it work?

格哈德-工作,效果相当surprisingly well. What was also surprising that the mice that were treated did not have severe side effects or actually no obvious side effects, we could not see any toxicities. What we saw is that the primary tumours were not invasive anymore and that these invasive cancer cells converted into fat cells and that the fat cells was essentially just sitting there like normal fat cells in the body. And as a consequence metastasis, so the seeding to distant organs, was also repressed.

Chris - What are the drugs that you use to do this?

Gerhard - So the drugs we used were two drugs. One is called rosiglitazone and it's used in the clinics for the treatment of diabetes and this drug is known to induce the conversion of stem cells into fat cells. The other drug is a cancer therapy called trametinib. It's an inhibitor of a signal that makes tumour cells divide and form more tumour cells.

Chris - And if one compares the outcomes for animals that did have this treatment and animals that didn't. How do the two result sets differ?

Gerhard - There are two major observations. The first one is that the animals that were control treated with the placebo treatment, they showed this highly invasive aggressive primary tumour invasion, and then metastasis mainly in the lungs whereas in the mice that were treated with rosiglitazone in combination with trametinib, we saw a loss of this invasion of malignant cancer cells into the surrounding tissue, also essentially no metastasis in the lungs anymore.

Chris - And if you look at the proportion of animals that responded was it nearly all of them or just a proportion?

Gerhard - It was all of them.

Chris - But the thing about cancer is that it is notoriously heterogeneous. If you look in cancer cells they all have a whole raft of different genetic changes because that's the nature of the beast we're dealing with. So how do you end up with all of the cells responding why don’t we get escape and some cells nonetheless come back and bring the cancer back because it bypasses the blockade that you're applying to it?

Gerhard - This is a very good question. This conversion of tumour cells into this aggressive invasive malignant cancer cells is relatively conserved in different cancer types. It's actually a program that is also used in embryonic development when certain cells have to migrate through the body to form organs. For example, during when the embryo forms and when the organs form. So we anticipate that this program of conversion to malignancy is well conserved in different cancer types and thus most cells will be targeted. And it's possible that even different cancer types can be targeted by the same therapy.