PMID- 15757447
OWN - NLM
STAT- MEDLINE
DCOM- 20060207
LR  - 20121115
IS  - 1744-8328 (Electronic)
IS  - 1473-7140 (Linking)
VI  - 5
IP  - 1
DP  - 2005 Feb
TI  - Matrix metalloproteinases in cancer: comparison of known and novel aspects of 
      their inhibition as a therapeutic approach.
PG  - 149-63
AB  - Matrix dissolution is a crucial step during tumor progression that converts a 
      premalignant cell to an overtly malignant one. Main players in this step are the 
      various matrix metalloproteinases (MMPs), which differ in substrate specificity 
      and tissue distribution, and thereby also differ in presence and function during 
      various stages of initial and systemic tumor spread. Accordingly, the inhibition 
      of MMP synthesis and/or activity represents novel potential therapeutic 
      strategies for the treatment of cancer patients. Considerable work has already 
      been carried out on synthetic inhibitors of MMP activity, but with little or even 
      adverse effects in recent clinical studies. The reasons may be inappropriate 
      patient populations in too advanced tumor stages, or inappropriate enzymes as 
      targets for inhibition. Upregulation of endogenous tissue inhibitors of MMP 
      (TIMPs) also provided ambiguous results, since TIMPs possess biologic functions 
      in addition to MMP inhibition, for example, TIMP-2 is a main player in the MMP-2 
      activation cascade. This may explain, at least in part, the adverse effects of 
      TIMP application/upregulation. Other strategies have been sought in order to 
      overcome these problems. These include the downregulation of MMP transcription by 
      cytokines. However, the effects of cytokines (other than MMP inhibition) may also 
      limit the use of this approach. Finally, empiric evidence for control and 
      modulation of MMP transcription and/or activation by several naturally occurring 
      substances, such as flavonoids, green tea polyphenols and curcumin, represent 
      novel options for the control of MMP activity even in early tumor stages. 
      Additionally, these substances have little or no toxic side effects and good 
      bioavailability, and therefore their continuing analysis provides intriguing 
      insight into tumor pathophysiology and possibly new therapeutic options.
FAU - Bachmeier, Beatrice E
AU  - Bachmeier BE
AD  - Department of Clinical Chemistry & Biochemistry, Surgical Clinic, 
      Ludwig-Maximilians-University Munich, Nussbaumstr. 20, D-80336 Munich, Germany.
FAU - Iancu, Cristina M
AU  - Iancu CM
FAU - Jochum, Marianne
AU  - Jochum M
FAU - Nerlich, Andreas G
AU  - Nerlich AG
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Expert Rev Anticancer Ther
JT  - Expert review of anticancer therapy
JID - 101123358
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Phenols)
RN  - 0 (Polyphenols)
RN  - 0 (Tea)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Disease Progression
MH  - Down-Regulation
MH  - Enzyme Inhibitors/pharmacology/*therapeutic use
MH  - Extracellular Matrix/metabolism
MH  - Flavonoids/chemistry/pharmacology
MH  - Humans
MH  - *Matrix Metalloproteinase Inhibitors
MH  - Matrix Metalloproteinases/*metabolism
MH  - Neoplasms/*drug therapy/*enzymology/physiopathology
MH  - Phenols/chemistry
MH  - Polyphenols
MH  - Tea/chemistry
RF  - 120
EDAT- 2005/03/11 09:00
MHDA- 2006/02/08 09:00
CRDT- 2005/03/11 09:00
PHST- 2005/03/11 09:00 [pubmed]
PHST- 2006/02/08 09:00 [medline]
PHST- 2005/03/11 09:00 [entrez]
AID - ERA050117 [pii]
AID - 10.1586/14737140.5.1.149 [doi]
PST - ppublish
SO  - Expert Rev Anticancer Ther. 2005 Feb;5(1):149-63. doi: 10.1586/14737140.5.1.149.