“Currently, 25% to 30% of adults in the United States are obese, which also causes fatty liver,” said Ekihiro Seki, MD, PhD, professor of Medicine and Biomedical Sciences at Cedars-Sinai and senior author of the study. “Our study found that fatty liver cells secrete cysts
and genetic material that promotes the spread of colorectal cancer to the liver, suggests that doctors should manage colorectal cancer patients with fatty liver differently.”
Seki noted that the study examined a mild form of fatty liver that clinicians may not be aware of or look for. He further emphasized that the condition is likely to be underdiagnosed.
“Among our patient samples, we noted that more than 40% of patients have fatty liver, but doctors often don’t order the specific MRI required to detect it, which means many cases are missed.”
Ultimately, 70% of patients with colorectal cancer will develop liver metastases (2✔ ✔Reliable Source
Liver Metastasis from Colorectal Cancer
According to Seki, go to the source, which is the main cause of death for these patients. He and other researchers sought to determine why some patients develop aggressive metastases while others do not, and why only some patients respond well to therapy.
“Our hypothesis was that fatty liver was doing something to cause these differences,” Seki said.
Associated with fatty liver and colorectal cancer
Seki and his team studied laboratory mice with colorectal cancer liver metastases that were fed a high-fat diet, which causes fatty liver. They noted that liver cells in mice with fatty livers produced more extracellular vesicles—particles that detach from cells and carry proteins and genetic material from the host cell.
“Extracellular vesicles produced by fatty liver cells contain three types of microRNAs that stimulate cancer proliferation, migration and invasion,” Seki said. “Cancer cells take up these extracellular vesicles, and this microRNA reacts with another protein called yes-related protein to promote tumor growth. Thus, the primary cancer in fatty liver mice becomes more aggressive and more metastatic.”
These yes-related proteins also suppress the Immune System in the immediate environment surrounding tumors, Seki says, making them resistant to common cancer-fighting immunotherapies.
Researchers found the same type of conditions when comparing tissue samples from human patients with colorectal cancer liver metastases and those with and without fatty liver.
Seki said further research is needed to investigate whether fatty liver has the same effect on cancer prevalence in lean patients, which is common in Asian populations. Further research may also help determine whether metastatic colorectal cancer is resistant to immunotherapy in patients with fatty liver and how this resistance can be reversed.
“We have ongoing efforts to target populations at high risk for fatty liver disease, and this study shows that we need to redouble our efforts, particularly in those with colorectal cancer,” said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer and FIRST PHASE Dear Chairman.
- Extracellular vesicles in fatty liver promote metastatic tumor microenvironment – (https://www.sciencedirect.com/science/article/abs/pii/S1550413123001407?via%3Dihub)
- Liver Metastasis from Colorectal Cancer – (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670263/)