Study finds colorectal cancer can signal the liver to produce a protein that contributes to muscle and bone wasting
Researchers at the University of Colorado Anschutz and Indiana University School of Medicine have identified a biological process that may help explain why colorectal cancer can cause severe muscle and bone loss, especially in its most advanced stages. The condition, known as cancer cachexia, can leave patients weak, make everyday activities more difficult and make it harder to tolerate cancer treatment.
The study published today in Nature Communications.
Researchers found that colorectal cancer cells can send a signal to the liver, causing it to produce a protein called IGFBP1. Once released into the bloodstream, IGFBP1 can contribute to the loss of muscle and bone.
In laboratory and mouse studies, blocking IGFBP1 helped preserve muscle and bone also improving muscle strength, even when the cancer itself remained.
"Our findings show that cancer can affect muscle and bone through a conversation between the tumor and the liver," said Andrea Bonetto, PhD, associate professor in the Department of Pathology and member of the CU Anschutz Cancer Center and the study's co-corresponding and senior author. "This gives us a new way to think about cancer-related wasting and a potential target for protecting patients from its effects."
How does cancer trigger muscle and bone loss?
The researchers found that colorectal cancer cells produce a protein called FGF21, which sends a signal to the liver. In response, the liver produces more IGFBP1, which enters the bloodstream and can directly contribute to muscle and bone loss throughout the body.
The researchers found higher levels of IGFBP1 in people with colorectal cancer than in healthy individuals. Levels were about twice as high in people with colorectal cancer, with particularly high levels in patients whose cancer had spread to the liver.
Laboratory experiments showed that IGFBP1 can cause muscle cells to shrink and increase the development of cells involved in breaking down bone.
What happened when researchers blocked IGFBP1?
When researchers blocked IGFBP1 in laboratory and preclinical models of colorectal cancer, the models retained more muscle and bone and had greater muscle strength.
Blocking the cancer-produced signal also reduced the liver's production of IGFBP1, helping protect against muscle and bone loss.
Importantly, blocking this pathway did not consistently reduce the amount of cancer in the models.
That finding suggests the approach could have a different goal from traditional cancer treatments. Instead of directly attacking the tumor, it could help protect the body from some of the damage caused by cancer.
"Since clinical and preclinical evidence already shows that preserving muscle mass can prolong life in cancer, our goal here is not necessarily to attack the tumor directly," said Bonetto. "It is to understand whether we can protect the patient from the damage cancer causes throughout the body, ultimately improving quality of life and survival".
Could this lead to a treatment?
The findings suggest that the FGF21-IGFBP1 pathway could eventually become a target for treatments designed to prevent or reduce cancer-related muscle and bone loss.
However, the research is still in its early stages. More studies are needed to determine whether blocking this pathway is safe and effective in people.
That will be particularly important because FGF21 and IGFBP1 also play roles in normal body functions, including metabolism.
"Our next challenge is to determine whether this pathway can be safely targeted in patients," Bonetto said. "If we can preserve muscle and bone, we may be able to help people remain stronger, more mobile and better able to tolerate cancer treatment."
Key points:
- Researchers at CU Anschutz and Indiana University identified a biological pathway that may contribute to muscle and bone loss in people with colorectal cancer.
- Colorectal cancer cells produce FGF21, which signals the liver to increase production of IGFBP1, a protein that can promote muscle and bone loss.
- Blocking IGFBP1 in laboratory research helped preserve muscle and bone and improved muscle strength, pointing to a potential new approach for protecting patients from cancer-related wasting.
