SCIENCE@home

Low-Anticoagulant Heparins in the Treatment of Metastasis

N. Rao,G. Prestwich,J. Hoidal,T. Kennedy

Published 2011 in Unknown venue

ABSTRACT

Metastasis is a spread of cancer cells to a distant location from the primary tumor. This process involves a complex series of events similar to those that occur during inflammation. The events of metastasis can be divided into four major steps. First, cancer cells proliferate and transform to acquire motility and ability to invade basement membrane to reach blood vessels. Second, cancer cells penetrate blood vessels due to increased vascular permeability facilitated by inflammatory mediators and enter the circulation. Third, in the circulation cancer cells are shielded by host cells (platelets and neutrophils) to escape surveillance by immune cells and survive shear forces of the bloodstream. Next, integrin-mediated arrest of circulating cancer cells occurs on the endothelial surface before extravasation. Once cancer cells extravasate, heparanase from cancer cells degrades heparan sulfates of the extra cellular matrix. The cleavage of heparan sulfates release growth factors that stimulate cancer cell growth as well as angiogenesis. The Receptor for Advanced Glycation Endproducts (RAGE) belongs to the immunoglobulin superfamily of cell surface molecules. The receptor’s name, RAGE, was coined for its ability to bind its first described ligand, advanced glycation end products (AGEs), which accumulate in physiological (aging) and pathological disorders such as diabetes (Schmidt et al., 1992). RAGE is a pattern recognition receptor for its ligation to structurally unrelated ligands that include Mac-1, HMGB1 and S100 /calgranulins. Similar to immunoglobulin, RAGE contains an extracellular structure with a V-type binding region and two C-type regions. Immediately following the C-type region is a transmembrane region and a short cytoplasmic domain (Fig. 1). The important roles played by RAGE in inflammation, diabetes, Alzhiemer’s disease and cancer have been discussed in detail (Ellerman et al., 2007; Logsdon et al., 2007; Schmidt et al., 2001; Sims et al., 2010; Tang et al., 2010). RAGE is ubiquitously expressed in tissues and inflammatory cells at low levels in homeostasis and its expression is increased in stress conditions. RAGE expression is observed in many tumors, including brain, breast, colon, lung, prostate, pancreatic, ovarian cancers, lymphoma and melanoma (Hsieh et al., 2003; Logsdon et al., 2007) and elevated levels of RAGE have been reported in colon (Sasahira et al., 2005), prostate (Ishiguro et al., 2005) and gastric cancers

PUBLICATION RECORD

  • Publication year

    2011

  • Venue

    Unknown venue

  • Publication date

    2011-09-12

  • Fields of study

    Medicine, Chemistry

  • Identifiers
    DOI 10.5772/19859
  • External record

    Open on Semantic Scholar

  • Source metadata

    Semantic Scholar

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-90 of 90 references · Page 1 of 1

CITED BY