Molecular mechanisms of hepatic metastasis in colorectal cancer.
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.


CONCLUSIONS
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.
Rudmik
L R
LR
Department of Surgery, University of Calgary, Alberta, Canada. Lukerudmik@shaw.ca
Magliocco
A M
AM
D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology; D010447:Peptide Hydrolases / Q000235:genetics / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D042442:Vascular Endothelial Growth Factors / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; C524898:PLAUR protein, human; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D042442:Vascular Endothelial Growth Factors; D018799:Intercellular Adhesion Molecule-1; D010447:Peptide Hydrolases; D020782:Matrix Metalloproteinases