Several types of cancer metastasize to the liver, a phenomenon that is generally associated with a low survival rate. Studies suggest that this preferential localization is caused by the pro-inflammatory action of hepatic cells. This inflammation creates an ideal host environment for the establishment and growth of metastases.
Although cancer is a very dangerous disease, it is very often possible to combat it successfully with the help of surgery, radiotherapy and/or chemotherapy when the tumor remains localized in a given organ. It is especially when cancerous cells break away from the main tumor and colonize other organs in the form of metastases that cancer becomes a real threat to survival. Moreover, approximately 90% of all cancer-related deaths are a direct consequence of the deadly impact of these metastases. In particular when they affect the organs essential to survival such as the brain, the lungs or the liver.
Metastases have their preferred organ to develop, including the liver
The establishment of metastases in a given organ remains one of the great mysteries of cancer biology. More than 130 years ago, the British physician Stephen Paget had already noticed that the location of metastases varied enormously depending on the type of cancer. He observed that breast cancers tend to metastasize to the liver, brain and lungs, while prostate cancer preferentially colonizes the bones.
To explain these differences, he proposed the “seed in the soil” model. According to this model, the formation of metastases requires not only the dispersion of cancer cells (the seed), but also the presence of an environment receptive to these cells (the compost) within a given organ.
The liver is particularly interesting for understanding this phenomenon. Indeed, this organ is a privileged site for the establishment of metastases from several types of cancer, in particular colorectal tumors. The blood vessels of the intestines are directly connected to the liver by the portal vein.
This close proximity means that approximately 70% of patients affected by advanced-stage colon cancer will develop liver metastases. However, several other metastatic cancers that are not in direct contact with the liver are located in this organ. In particular those of the breast, esophagus, stomach, pancreas, lung, kidney and skin (melanomas). It is therefore clear that the liver has certain characteristics which make it more susceptible to colonization by circulating metastatic cells.
Inflammation promotes the proliferation of metastases in the liver
The results of a preclinical study published in the prestigious Nature allow for the first time to better understand this phenomenon. Using a pancreatic tumor model in mice, the researchers first showed that the presence of the tumor caused systemic inflammation.
Caused by the secretion of an inflammatory molecule into the circulation (interleukin-6). Liver cells (hepatocytes) respond to this signal by producing a class of fibrous proteins (serum amyloid A or SAA). By depositing close to cells, creates a matrix that promotes adhesion of inflammatory immune cells and circulating cancer cells.
Inflammation is the breeding ground for metastases
In other words, the propensity of cancer cells to locate in the liver is directly linked to an inflammatory response of hepatocytes to the presence of a tumor in the body. This mechanism allows it to orchestrate the production of a breeding ground favorable to the implantation of metastases. An analysis done on patients with pancreatic or colon cancer with liver metastases shows an increase in SAA levels. The greater the increase, the lower the chances of survival.
These results therefore suggest that the development of therapeutic means to suppress the inflammatory response in the liver and this production of AAS could prevent the formation of liver metastases in people affected by cancer.
Reduce inflammation by adopting a healthy lifestyle
In the meantime, it should be remembered that other metabolic conditions can influence the production of interleukin-6 and the development of inflammatory conditions that may increase the susceptibility of the liver to metastasis. The most important being obesity. Maintaining a healthy weight, adopting a plant-rich diet and staying active are still the best way to reduce chronic inflammation to reduce the risk of cancer and improve the chances of survival for people with the disease. .
Lee JW et al. Hepatocytes direct the formation of a pro-metastatic niche in the liver. Nature 567: 249-252.