The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia.
In the past decades, a lot of effort has been put in identifying the role of matrix metalloproteinases (MMPs) in cancer. The main role of MMPs in angiogenesis, tumor growth and metastasis is degradation of extracellular matrix (ECM) and release and/or activation of growth factors through their degradative activity. The degradative activity finally results in cancer progression. MMP-inhibitors (MMPIs) have already been designed and tested, based on the degradative role of MMPs in cancer progression. First clinical trials with MMPIs have been performed with disappointing results, showing that in order to use MMP-inhibition the mechanisms underlying MMP-expression in cancer have to be further elucidated. This paper reviews the mechanisms of MMPs on molecular and cellular level and discusses the role for MMPs and MMP-inhibition in cancer with special focus on acute leukemia.
Klein
G
G
Division of Pediatric Oncology and Hematology, Beatrix Children's Hospital, Groningen University Hospital, Hanzeplein 1, P.O. Box 30.001, Groningen 9700 RB, The Netherlands.
Vellenga
E
E
Fraaije
M W
MW
Kamps
W A
WA
de Bont
E S J M
ES
D000208:Acute Disease; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology
D061965:Matrix Metalloproteinase Inhibitors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9