Matrix metalloproteinases in colorectal cancer: is it worth talking about?
Matrix metalloproteinases (MMPs), a family of extracellular matrix degrading enzymes, are expressed in various stages of colorectal cancer (CRC) and correlate with survival and prognosis. There is considerable evidence in preclinical models that MMP inhibitors (MMPIs) are effective at multiple stages of CRC tumor progression, including reducing the number of intestinal adenomas, inhibiting the growth and establishment of primary CRC tumors, and reducing metastasis to the lung and liver. However, clinical trials with MMPIs in other tumor types have been largely unsuccessful, raising the question as to whether MMPs represent therapeutic targets in CRC. This review focuses on the expression, role, and contribution of MMP family members to various stages of CRC tumor progression. The conclusion is that there is considerable evidence to suggest that MMP inhibition may be an effective strategy if applied at either end of the tumor progression spectrum; the prevention of adenomas, or the treatment of micrometastatic disease.
Department of Cancer Biology, Vanderbilt University, 771 Preston Research Building, 23rd and Pierce Avenue, Nashville TN 37232, USA.
Rebecca A
RA
Wagenaar-Miller
Lee
L
Gorden
Lynn M
LM
Matrisian
D000236:Adenoma / Q000378:metabolism; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000201:enzymology*; D018450:Disease Progression; D006801:Humans; D007410:Intestinal Diseases / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D011379:Prognosis; D017434:Protein Structure, Tertiary
D020782:Matrix Metalloproteinases