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Researchers from the Abramson Cancer Center of the University of Pennsylvania report in Nature why the liver is the most common site of metastatic disease. The research shows that hepatocytes coordinate myeloid cell accumulation and liver fibrosis (the thickening and scarring of tissue) which increases the organ’s susceptibility to cancer cells.



"While it is well known that the liver is a common site of cancer spread, the underpinnings of how this occurs have largely remained elusive. Our study identifies hepatocytes as major initiators of this process and show several key steps in this process." explains Gregory L. Beatty, corresponding author of the study.



"Understanding this biology is the first step toward knowing how to disrupt it. If we can prevent the liver from being supportive of cancer spread, that could have major implications for patients as metastasis is the major cause of cancer-related death."





What are hepatocytes?

Hepatocytes are

Hepatocytes are parenchymal cells that comprise the main unit of the liver and are responsible for most of the organ’s metabolic functions.

Study approach and findings

Attraction of myeloid cells which dampen the immune response

Activation of hepatic stellate cells which deposit extracellular matrix material (this acts as an anchor and sustenance to cancer cells)

These changes create what is known as a “pro-metastatic niche”. The team showed that it is possible to inhibit the process by blocking the signaling components (IL-6, STAT3, SAA proteins), disrupting the signaling pathway. This limited the cancer’s ability to metastasize to the liver.



The team were also able to demonstrate, through a collaboration with investigators at the Mayo Clinic Arizona and other Penn colleagues, that patients with liver metastases originating from the pancreas, as well as other types of primary tumor (lung, colorectal) had an elevated level of SAA proteins in the bloodstream.





Additional findings

Lee, J. W., et al. Hepatocytes direct the formation of a pro-metastatic niche in the liver. Nature (2019) DOI: 10.1038/s41586-019-1004-y

Hepatocytes direct the formation of a pro-metastatic niche in the liver. (2019) DOI: 10.1038/s41586-019-1004-y Maitra, A. Molecular envoys aid cancer spread. News and Views. Nature (2019) DOI: 10.1038/d41586-019-00710-z



