Like a weed spreading seeds before it’s even sprouted from the soil, breast cancer cells can migrate around the body before any lumps can be felt or detected by a mammogram, two mouse studies show.
Each proposes an explanation why early disseminating cancer cells – cells that “spread” around the body when the tumour is only microscopic – are better at invading distant tissues than those from an advanced tumour.
Both studies, published in Nature, could lead to new ways of monitoring cancer’s spread.
“They have such firm support that early dissemination is really occurring much more than we thought,” Rik Thompson, breast cancer biologist from the Queensland University of Technology in Australia and who was not involved in the study, says.
Metastasis – the formation of secondary tumours as a result of disseminating cells – is responsible for most cancer-related deaths.
And while the idea that early disseminating cancer cells lead to metastasis is nothing new, the question of why hasn’t yet been fully answered.
A protein called HER2 is overproduced in roughly 25% of breast cancer cases. In those patients, the chance their cancer will reappear increases three-fold.
Both teams of researchers investigated HER2-positive cancer but told two different stories.
Hedayatollah Hosseini from the University of Regensburg in Germany and his colleagues suggest the female hormone progesterone drives the circulation of early cancer cells from microscopic tumours.
Meanwhile, Kathryn Harper from the Icahn School of Medicine at Mount Sinai in the US and her colleagues showed the HER2 protein itself helped early invasive cells enter the bloodstream.
Thompson says that neither paper is more convincing than the other – they’re simply different, and challenge the common notion that cancer cells are better at spreading when they originate from an advanced tumour.
Harper’s team hooked up a microscope to mice mammary glands and watched its cancer cells in the lining tissue. They also studied human bone marrow samples seeded with disseminated cancer cells.
And they found that HER2 switches on another protein, which in turn subdues a cancer-halting enzyme called p38. The cancer cells were able to circulate the body unhindered.
On the other hand, Hosseini and colleagues turned to progesterone.
Using human tissue samples, the researchers showed that progesterone triggers a cell to release two proteins that target and strengthen an invasive cells’ ability to migrate.
Thompson is curious about a possible connection between the two studies – specifically p38 from Harper’s study and progesterone from Hosseini’s.
“Clearly they’re both working on the same model on early stage dissemination, but the connection between the two is an intriguing question for me,” he says. Perhaps progesterone regulates p38 – or the other way around.
And in the short term, the researchers suggest HER2-positive breast cancer patients may benefit from close blood monitoring early on to catch any tumours that might grow from metastasising cells.
Read science facts, not fiction...
There’s never been a more important time to explain the facts, cherish evidence-based knowledge and to showcase the latest scientific, technological and engineering breakthroughs. Cosmos is published by The Royal Institution of Australia, a charity dedicated to connecting people with the world of science. Financial contributions, however big or small, help us provide access to trusted science information at a time when the world needs it most. Please support us by making a donation or purchasing a subscription today.