Table 2.

HMGB1 and RAGE in Cancer and Inflammation

Inflammatory state, disease or cancer	Effect of RAGE/HMGB1
Colon cancer	Co-expression of RAGE and HMGB1 leads to enhanced migration and invasion by colon cancer cell lines. Increased RAGE expression in colon cancer has been associated with atypia, adenoma size, and metastasis to other organs. Stage I tumors have relatively low % of tumors expressing, Stage IV virtually universal expression
Prostate cancer	Co-expression of RAGE and HMGB1 has been found in a majority of metastatic cases, in tumor cells and associated stromal cells.
Pancreatic cancer	Enhanced expression of RAGE and HMGB1 in the setting of metastases.
Lung and esophageal cancers	Higher tumor stage is characterized by downregulation of RAGE.
Inflammatory Arthritis	HMGB1 is overexpressed. RAGE binding, as other receptors, results in: macrophage stimulation, induction of TNFα and IL-6, maturation of DCs, Th1 cell responses, stimulation of CD4+ and CD8+ cells, and amplification of response to local cytokines.
Sepsis	HMGB1 propagates inflammatory responses and is a significant RAGE ligand in the setting of sepsis and acute inflammation. HMGB1 is an apparent autocrine/paracrine regulator of monocyte invasion, involving RAGE mediated transmigration through the endothelium.