If a cancer spreads, it often spreads to the liver. And the way healthy liver cells respond to inflammation could explain the organ’s susceptibility to this spread, according to new research in mice.
Researchers at the University of Pennsylvania in the US have pinpointed cells in the livers of mice, called hepatocytes, that create an environment cancer cells might need to settle and grow there.
“The liver is an important sensor in the body,” said Dr Jae W. Lee, lead researcher on the study. “We show that hepatocytes sense inflammation and respond in a structured way that cancer uses to help it spread.”
The study, published in Nature, offers clues about how this chain reaction might be prevented, suggesting future avenues of research into limiting the spread of cancer to the liver.
‘Seed and soil’
The research sheds light on the well-documented ‘seed and soil’ theory of how cancer cells spread around the body. The idea is that the cellular ‘seeds’ of secondary cancers require a fertile ‘soil’ in other organs in which to grow.
“The seed and soil hypothesis is well-recognised, but our research now shows that hepatocytes are the major orchestrators of this process,” says Professor Gregory Beatty, senior researcher on the study.
Professor Robert Insall, from the Cancer Research UK Beatson Institute explained that researchers now know cancer cells don’t spread as previously thought and require a supportive environment in which to grow.
“If the cancer cells can’t find the right conditions to settle and grow, they either pass harmlessly by or die,” he said.
“For a new secondary tumour to form, something needs to change so that the travelling cancer cells land in a site that supports them and allows them to grow.”
The US team believe they’ve pinpointed a possible chain reaction in the liver that causes this supportive environment to be created, with liver cells called hepatocytes controlling the process.
Based on studies in mice with pancreatic cancer, the research found that hepatocytes respond to inflammation by activating a protein called STAT3, which in turn increases their production of other proteins called SAA.
The SAA proteins then recruit immune cells that change the liver, creating the supportive ‘soil’ the cancer cells need to settle and grow in mice.
But the research showed that molecules capable of blocking the chain reaction could reduce cancer cells’ ability to spread to the liver in mice.
As Professor Insall adds: “This paper shows how normal, non-cancerous liver cells can attract a group of normal white blood cells that cooperate to make a supportive environment for cancer cells.
“The result is that any cancer cells that land nearby will be supported and will grow to form secondary tumours. It could perhaps also explain why liver metastases are so common.
“It might also offer future pathways to stop cancer from spreading, by blocking new niches from being created.”
Lee, J et al. (2019) Hepatocytes direct the formation of a pro-metastatic niche in the liver. Nature DOI: 10.1038/s41586-019-1004-y