Hypoxia-induced HMGB1 expression of HCC promotes tumor invasiveness and metastasis via regulating macrophage-derived IL-6
- Shanghai Institute of Medical Imaging, Shanghai (China)
- Department of Interventional Radiology, Fudan University Shanghai Cancer Center, Shanghai (China)
Highlights: • Hypoxia heightens HMGB1 expression in HCC via HIF1α. • Elevated HMGB1 exacerbates macrophage infiltration into tumor under hypoxia. • Macrophage-derived IL-6 promotes EMT of HCC cells under hypoxia. • Inhibition of HMGB1 attenuates tumor metastasis and macrophage infiltration. 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.
- OSTI ID:
- 23082375
- Journal Information:
- Experimental Cell Research, Vol. 367, Issue 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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