a hormones Separated by fat cells can stop development of liver tumors In rats, according to a new study from the Life Sciences Institute of the University of Michigan (United States), as published in the journal Cell Metabolism.
Provide proof of concept for developing results Hepatocellular Carcinoma Treatmentmost common form of liver cancer,
Researchers used mice as a model to study how Molecular and Cellular Changes are affected by fatty liver disease Non-alcoholic, and how the disease progresses as a result of these changes.
Although it starts as a relatively benign accumulation of fat in the liverThe disorder can develop into non-alcoholic steatohepatitis (NASH), which Increases risk of liver cancer,
Liver has dozens of types different cellsincluding various immune cells.
Thanks to single-cell RNA sequencing, a technology that makes it possible to investigate single cell gene expression In complex tissues, the researchers previously created an atlas of liver cells and a map of intracellular signaling in the liver of healthy and NASH mice.
For this latest study, scientists wanted to identify molecular change NASH is specialized in the state that alters the balance and interactions of these cell types as much as possible. therapeutic target To reverse the progression of NASH to cancer.
Liver cancer in patients with NASH is different cancer caused by viral hepatitisas it often develops in the absence of liver cirrhosis,” says Jiandi Lin, a faculty member at the UM Life Sciences Institute and lead author of the study. We suspect that in liver cancer Related to NASH, different disease mechanisms may be involved”.
Lin and his colleagues observed changes in two types of immune cells In particular they appear to contribute to the development of HCC.
In the liver of NASH mice, T cells – the immune cells symptoms that usually fight off infected or damaged cells, such as cancer cells functional impairment,
At the same time, the team found that a second type immune cellscalled macrophages, acquired molecular features usually associated with cancer,
“These Change what we see in macrophages and T cells are similar tumor microenvironmentbut they are also before cancer appears Lin, who is also a professor of cell and developmental biology at the U-M School of Medicine. This gives us a clue that perhaps these changes may occur in the microenvironment of the liver. provide fertile land presence and development cancer cells Of liver. It almost seems as if the liver, once it develops NASH, is already setting itself up for cancer cells to thrive.”
The team also identified a hormone that acts as a check point disease progression, and appears to potential as a treatment: La Neuregulina 4 (NRG4).
Lin’s team previously revealed that NRG4 – a hormone secreted mainly by Cells fat can protect the liver against NASH of rats, and that a lack or loss of this hormone leads to more severe levels of liver disease,
Now the team has found that hormones can suppress carcinoma Hepatocellularity in rats with NASH. Their results suggest that mice that lack the NRG4 hormone develop NASH. develops More severe and more liver tumors compared to mice with normal levels of NRG4.
when scientists increased hormone levels In mice – either by genetically increasing NRG4 expression in adipose tissue or by treating mice with a recombinant NRG4 fusion – the increase in NRG4 levels was suppressed liver cancer progression Nash.
“Many studies liver cancer focus on oneself cancerous liver cells: how they grow and how they evade the immune system,” says Lin. But our findings break this structure focused on the livershowing that a fat derived hormones can actually reprogram the liver environment and have a huge impact on the development of liver cancer.”
they state that more research needed Before being used as NRG4 carcinoma therapy liver cells. Lin and his team now plan to investigate the approaches increase hormone effectiveness You better understand nature which underlies its regulation of macrophages and T cells in the liver.