Role of the microenvironment in liver metastasis: from pre- to pro-metastatic niches
Cet article passe en revue les travaux récents sur le rôle du micro-environnement dans la formation et la croissance de métastases hépatiques
Liver metastases remain a major barrier to successful management of malignant disease, particularly for cancers of the gastrointestinal (GI) tract but also for other malignancies such as breast carcinoma and melanoma. The ability of metastatic cells to survive and proliferate in the liver is determined by the outcome of complex, reciprocal interactions between the tumor cells and different local resident subpopulations including the sinusoidal endothelium, stellate, Kupffer and inflammatory cells that are mediated through cell-cell and cell-extracellular matrix adhesion and the release of soluble factors. Cross communication between different hepatic resident cells in response to local tissue damage and inflammation and the recruitment of bone marrow cells further enhance this inter-cellular communication network. Both resident and recruited cells can play opposing roles in the progression of metastasis and the balance of these divergent effects determines whether the tumor cells will die, proliferate and colonize the new site or enter a state of dormancy. Moreover, this delicate balance can be tilted in favor of metastasis, if factors produced by the primary tumor pre-condition the microenvironment to form niches of activated resident cells that promote tumor expansion. This review aims to summarize current knowledge on these diverse interactions and the impact they can have on the clinical management of hepatic metastases.