Molecular mechanisms of hepatic metastasis in colorectal cancer

J Surg Oncol. 2005 Dec 15;92(4):347-59. doi: 10.1002/jso.20393.

Abstract

Background: Colorectal cancer currently accounts for 11% of all cancers in the United States and is the second leading cause of cancer-related death, with the majority of deaths attributable to hepatic metastases. Many new studies are elucidating the complex molecular factors involved in this event, which could be used to generate clinically applicable screening and therapeutic tools.

Methods: An initial Pubmed and Medline literature search using keywords such as, molecular factor, colorectal cancer, hepatic metastasis/es, and main headings, such as angiogenesis, was reviewed. Since there are many molecular factors involved in this process not all could be included in this review. The list of discussed gene products was limited to the most studied factors, identified by the number of references in the literature search, and additional recently discovered gene products with in-vivo evidence of strong metastasis association.

Results: Twenty molecular factors were identified and included in the discussion of this review article. The molecular factors were separated into four groups based on their function, they are: proteolysis, adhesion, angiogenesis, and cell survival. All factors have a promising role as a screening or therapeutic target.

Conclusion: This review has identified the many recent advances in elucidating the pathways involved in colorectal cancer hepatic metastasis. By better understanding the many complex molecular events involved in metastasis, novel screening and therapeutic tools may be developed with the ultimate goal of preventing metastasis and increasing patient survival.

Publication types

  • Review

MeSH terms

  • Apoptosis Regulatory Proteins / physiology
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms / blood supply
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / physiology
  • Membrane Glycoproteins / physiology
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / pathology
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / physiology*
  • Receptors, CXCR4 / metabolism
  • Receptors, Cell Surface / physiology
  • Receptors, Urokinase Plasminogen Activator
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / physiology
  • Vascular Endothelial Growth Factors / physiology

Substances

  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • PLAUR protein, human
  • Receptors, CXCR4
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factors
  • Intercellular Adhesion Molecule-1
  • Peptide Hydrolases
  • Matrix Metalloproteinases