title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Oncology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, China Department of Oncology, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Oncology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Daping
authors.initials: D
authors.lastname: Zhong
authors.affiliation: Department of Oncology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology and Southwest Cancer Centre, Southwest Hospital, Third Military Medical University, Chongqing, China lianghoujie@sina.com.
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
mesh_terms: D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014162:Transfection; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D016328:NF-kappa B; D042582:Vascular Endothelial Growth Factor C
keywords: High-mobility group box 1 protein; colon cancer; lymphangiogenesis; metastasis; nuclear factor-κB; vascular endothelial growth factor C