Non-histone nuclear factor HMGB1 as a therapeutic target in colorectal cancer

Expert Opin Ther Targets. 2011 Feb;15(2):183-93. doi: 10.1517/14728222.2011.546785. Epub 2011 Jan 5.

Abstract

Introduction: High-motility group box (HMGB)-1 is the focus of recent cancer research. HMGB1 plays a critical role in cancer development, progression, and metastasis by activation of cancer cells, enhancement of tumor angiogenesis, and suppression of host anti-cancer immunity. HMGB1 is a relevant target for cancer treatment.

Areas covered: This review aims to overview the biological feature and diverses role in cancer of HMGB1. HMGB1 is a non-histone chromosomal protein, a secretory protein binding to the receptor for advanced glycation end products in cancer cells and monocyte-lineage immune cells, and a DNA presenting chaperon for toll-like receptors. HMGB1 enhances proliferation, motility, invasion and survival of cancer cells. In contrast, HMGB1 induces apoptosis in monocyte-lineage immune cells and inhibits tumor-infiltrating macrophages and dendritic cells, lymph node sinus macrophages and liver Kupffer cells to attenuate anti-cancer immune responses and anti-metastatic organ defense. Then the novel techniques for inhibiting HMGB1 are reviewed.

Expert opinion: Various techniques targeting HMGB1 are subjected to trial. HMGB1 targeting is a potential therapeutic techniqueagainst cancer development, progression, and especially metastasis. Technical breakthroughs in application of HMGB1 targeting to human diseases are now urgently required.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Dendritic Cells / metabolism
  • Glycation End Products, Advanced / metabolism
  • HMGB1 Protein / antagonists & inhibitors*
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Histones / metabolism
  • Humans
  • Kupffer Cells / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Molecular Targeted Therapy*
  • Neoplasm Metastasis / drug therapy*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / metabolism
  • Toll-Like Receptors / metabolism

Substances

  • Glycation End Products, Advanced
  • HMGB1 Protein
  • Histones
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Toll-Like Receptors