Journal
EXPERIMENTAL CELL RESEARCH
Volume 367, Issue 1, Pages 81-88Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2018.03.025
Keywords
Hypoxia; HMGB1; Metastasis; Macrophage; Hepatocellular carcinoma
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Funding
- National Natural Sciences Foundation of China [81501562]
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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-1 alpha-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.
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