Inflammation-associated premetastatic niche formation

Metastasis remains the leading cause of cancer-related death. In 1889, Stephen Paget originally proposed the theory “seed-and-soil.” Both cancer cell-intrinsic properties (“seed”) and fertile microenvironment (“soil”) are essential for metastasis formation. To date, accumulating evidences supported the theory using mouse models. The formation of a premetastatic niche has been widely accepted as an accel for metastasis. Similar to tumor microenvironment, various types of cells, such as immune cells, endothelial cells, and fibroblasts are involved in premetastatic niche formation. We have discovered that primary tumors hijack Toll-like receptor 4 (TLR4) signaling to establish a premetastatic niche in the lung by utilizing the endogenous ligands. In this review, we discuss the mechanisms that underlie inflammation-associated premetastatic niche formation upon metastasis, focusing especially on myeloid cells and macrophages as the cells executing and mediating complicated processes.