A couple of week’s ago we looked at how being obese can give cancer a helping hand. I thought this would be useful as most people know there is a link but perhaps not much more than that. The message had two simple parts: (1) When we make extra fat cells they change the metabolism of our bodies through chemical signals that wander around and, in passing, can also drive cancer growth, and (2) Some of the extra fat cells congregate around tumours and give them direct positive vibes (i.e. other, local chemical signals).
But you may have spotted that I didn’t actually say what these ‘signals’ are – for the very good reason that we know rather little about them. Step forward, right on cue, Ines Barone, Suzanne Fuqua and friends from the University of Calabria and Baylor College of Medicine, Houston with a wonderful paper that’s just been published. Wonderful because it’s got so much data I’m green with envy but also because, like most excellent science papers, the key message is simple: normal cells that have moved into the neighbourhood can indeed talk directly to tumour cells. And the messenger is … leptin!
That’s astonishing. Even those with only a smattering of knowledge about how we work will know that leptin plays a key role in regulating energy balance. It’s a protein – a hormone – that circulates in our blood at levels roughly proportional to body fat. Its job is to signal the ‘full’ state, i.e. to reduce appetite. Somewhat perversely, obesity usually causes abnormally high leptin levels but it doesn’t work very well because the body has become resistant to its signal – much as happens with insulin in type 2 diabetes.
The new results show that leptin, released from nearby cells, can bind to cancer cells and make them do two things: (1) Release a chemical that tells the adjacent cells to send out even more leptin, and (2) Make proteins that help the tumour cells grow and invade.
There are a few wrinkles to these results. The study was on breast cancer cells with a particular mutation (in a receptor for the hormone estrogen) and the ‘groupies’ providing the leptin turned out not to be fat cells but fibroblasts – part of the supportive framework of cells and tissues – so they’re ‘cancer-associated fibroblasts’ (CAFs). And when the CAFs release leptin it floods out and the tumour cells embrace it and make yet more receptors for leptin to bind to on their surface.
But these details matter less than the key point: for at least some types of cancer cell a hormone often made in excessive amounts in obesity can signal directly to tumour cells, telling them to grow and spread. This doesn’t mean that all breast tumours, yet alone all cancers, respond to leptin. What it does show is that a key factor in obesity can talk directly to some types of tumour cell. It’s another example of the painstaking way in which science usually proceeds and, assuming the results are reproducible, we have one more little bit of the jig-saw.