The Hepatic Pre-Metastatic Niche

SIMPLE SUMMARY: The pre-metastatic niche is a recently established concept that could lead to targeted therapies that prevent metastasis before ever occurring. Considering that 90% of cancer mortality results from metastasis, the PMN is thus a salient opportunity for intervention. The purpose of the current review is to cover what is known specifically about the hepatic pre-metastatic niche, a topic that has garnered increasing research focus within the last decade. We discuss the methods of communication between primary tumors and the liver, the involved cell populations, the key changes within liver tissue, and perspectives on the future of the field. ABSTRACT: Primary tumors can communicate with the liver to establish a microenvironment that favors metastatic colonization prior to dissemination, forming what is termed the “pre-metastatic niche” (PMN). Through diverse signaling mechanisms, distant malignancies can both influence hepatic cells directly as well as recruit immune cells into the PMN. The result is a set of changes within the hepatic tissue that increase susceptibility of tumor cell invasion and outgrowth upon dissemination. Thus, the PMN offers a novel step in the traditional metastatic cascade that could offer opportunities for clinical intervention. The involved signaling molecules also offer promise as biomarkers. Ultimately, while the existence of the hepatic PMN is well-established, continued research effort and use of innovative models are required to reach a functional knowledge of PMN mechanisms that can be further targeted.