Regulation of matrix metalloproteinase (MMP) activity by the low-density lipoprotein receptor-related protein (LRP). A new function for an "old friend".
Matrix metalloproteinases (MMPs) are essential contributors to a microenvironment that promotes tumour progression. During the two last decades, inhibition of MMPs has become the focus of considerable interest for cancer therapy, and numerous synthetic metalloproteinase inhibitors have been developed by the pharmaceutical industry. However, clinical trials have shown disappointing efficacy or unexpected toxicity and new targets are thus eagerly awaited. The identification of endocytic clearance of several MMPs by the low-density lipoprotein receptor-related protein (LRP) might provide insight into novel strategies for controlling MMP level during malignant processes. This review attempts to summarize recent aspects on the cellular and molecular basis of LRP-mediated endocytic disposal of MMPs.
Emonard
Hervé
H
CNRS UMR 6198, IFR 53, Faculté de Médecine, 51, rue Cognacq Jay, 51095 Reims cedex, France. herve.emonard@univ-reims.fr
Bellon
Georges
G
de Diesbach
Philippe
P
Mettlen
Marcel
M
Hornebeck
William
W
Courtoy
Pierre J
PJ
D000818:Animals; D015536:Down-Regulation; D004705:Endocytosis; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D000099262:Thrombospondin 2
D026502:LDL-Receptor Related Proteins; D020782:Matrix Metalloproteinases; D011498:Protein Precursors; D019700:Thrombospondin 1; D019699:Thrombospondins; D019716:Tissue Inhibitor of Metalloproteinase-2; D000099262:Thrombospondin 2