Inflammatory networks cultivate cancer cell metastasis to the liver

The liver is the most frequent site of metastatic spread in malignancies that arise from the digestive system, including pancreatic ductal adenocarcinoma (PDAC). Metastasis to the liver is a major cause of morbidity and mortality in cancer patients, yet mechanisms that govern this process remain poorly understood. Until recently, liver tropism of metastasis was believed to be driven by mechanical factors that direct the passive flow of circulating cancer cells to the liver. However, emerging evidence now shows that liver metastasis is a dynamic process that is, at least in part, dependent on the formation of a "pro-metastatic niche". Key features of this niche are myeloid cells and fibrosis that support cancer cell colonization and growth. Inflammatory responses that are mounted early during primary tumor development are critical for the recruitment of myeloid cells and the deposition of extracellular matrix (ECM) proteins within the liver. Intriguingly, the inflammatory processes that direct the formation of a pro-metastatic niche share remarkable resemblance to mechanisms of liver injury and regeneration, suggesting that cancer co-opts physiological liver functions to support metastasis. Therefore, therapeutic strategies that target key elements of liver inflammation that form the basis of a pro-metastatic niche may lead to effective treatments for metastatic cancer.