Metalloproteinases: role in breast carcinogenesis, invasion and metastasis.
The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix. Currently, at least 19 members of this family are known to exist. Based on substrate specificity and domain organization, the MMPs can be loosely divided into four main groups: the interstitial collagenases, gelatinases, stromelysins and membrane-type MMPs. Recent data from model systems suggest that MMPs are involved in breast cancer initiation, invasion and metastasis. Consistent with their role in breast cancer progression, high levels of at least two MMPs (MMP-2 and stromelysin-3) have been found to correlate with poor prognosis in patients with breast cancer. Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing breast cancer and in blocking metastasis of established tumours
Department of Nuclear Medicine, St Vincent's Hospital, Dublin, Ireland. Michael.J.Duffy@ucd.ie
M J
MJ
Duffy
T M
TM
Maguire
A
A
Hill
E
E
McDermott
N
N
O'Higgins
D017209:Apoptosis; D001485:Basement Membrane / Q000378:metabolism; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000201:enzymology; D011379:Prognosis; D011480:Protease Inhibitors / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D017978:Receptors, Growth Factor / Q000378:metabolism; D013379:Substrate Specificity
D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D017978:Receptors, Growth Factor; D008666:Metalloendopeptidases