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Objectives   To investigate the roles of high-mobility group box 1 (HMGB1) protein in lymphangiogenesis and lymphatic node metastasis in colon cancer.Methods   Archival tumour specimens from patients with colon cancer were analysed in this retrospective immunohistochemical study. HMGB1, vascular endothelial growth factor C (VEGF-C) and podoplanin protein levels were analysed immunohistochemically . In vitro studies using the colon cancer cell line HCT116 were also undertaken to investigate the relationship between HMGB1, VEGF-C and nuclear factor (NF)-κB.Results   Specimens from 70 patients with colon cancer were reviewed. The presence of positive HMGB1 immunohistochemical staining significantly correlated with lymphatic microvessel density, lymph node metastasis and VEGF-C immunohistochemical staining in colon cancer specimens. The presence of positive VEGF-C immunohistochemical staining significantly correlated with lymph node metastasis. The in vitro studies demonstrated that HMGB1 upregulated VEGF-C mRNA and protein in a dose-dependent manner in HCT116 cells, and that this was mediated via NF-κB.Conclusions   HMGB1 immunohistochemical staining was significantly associated with lymphangiogenesis and lymphatic node metastasis in colon cancer. There was evidence that HMGB1 upregulates VEGF-C by activating NF-κB in a colon cancer cell line.

journal of international medical research

High-mobility group box 1 protein activating nuclear factor-κB to upregulate vascular endothelial growth factor C is involved in lymphangiogenesis and lymphatic node metastasis in colon cancer