CXCL1 Is Critical for Premetastatic Niche Formation and Metastasis in Colorectal Cancer.

ABSTRACT: Emerging evidence suggests that the primary tumor influences the development of supportive metastatic microenvironments, referred to as premetastatic niches, in certain distant organs before arrival of metastatic cells. However, the mechanisms underlying the contributions of the primary tumor to premetastatic niche formation are not fully understood. Here, we demonstrate that colorectal carcinoma cells secrete VEGFA, which stimulates tumor-associated macrophages to produce CXCL1 in the primary tumor. Elevation of CXCL1 in premetastatic liver tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a premetastatic niche that ultimately promoted liver metastases. Importantly, premetastatic liver-infiltrating MDSCs induced tumor cell survival without involvement of inna

SUBMITTER: Wang D 

PROVIDER: S-EPMC5877403 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature