Interactions in the (Pre)metastatic Niche Support Metastasis Formation

Abstract

Metastasis formation is the leading cause of death in cancer patients. Thus, understanding and targeting this process is an unmet need. Crucial steps during the establishment of metastases include the (pre)metastatic niche formation. This process relies on the interaction of the primary tumor with the environment of distant organs (premetastatic niche) and the interaction of cancer cells with their environment when arriving in a distant organ (metastatic niche). Here, we summarize the current knowledge on the interactions in the tumor environment that result in (pre)metastatic niche formation, specifically in the context of tumor secreted factors, extracellular matrix, immune as well as stromal cells, and nutrient availability. We further highlight strategies to disrupt these interactions as therapeutic interventions against metastases.

Keywords: extracellular matrix; immune cells; metastatic niche; nutrient environment; premetastatic niche; stromal cells; tumor environment; tumor secreted factors.

Figure 1

Establishment and interactions in the (pre)metastatic niche. (A) Premetastatic niche formation depends on the interaction of tumor secreted factors with the local environment of a distant organ. (B) Metastatic niche formation requires the interaction of cancer cells with the local environment. Red indicates inhibition, green indicates activation, blue thick arrows indicate recruitment.