Article ID Journal Published Year Pages File Type
8450787 Experimental Cell Research 2018 25 Pages PDF
Abstract
Hypoxia is associated with the progression of hepatocellular carcinoma through promotion of spontaneous metastasis but the mechanism remains unclear. Here, we hypothesis that tumor cell-derived HMGB1 orchestrates macrophages infiltration and promotes metastasis of HCC via enhancing macrophage-secreted IL-6 under hypoxia. HMGB1 expression was robustly exacerbated in tumors of HCC patients with PVTT. Meanwhile, hypoxia exposure gave rise to HMGB1 expression in hepatoma cells of human and mouse in a HIF-1α-dependent manner and subsequently induced the infiltration and reprogramming of macrophages to augment the expression of Il-6. Further study demonstrated macrophage-derived IL-6 enhanced the invasiveness and metastasis of murine HCC cells. Therefore, our study provides a novel understanding of the relationship between tumor cells and tumor associated macrophages (TAMs) in the context of hypoxia.
Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
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