PMID- 15588763
OWN - NLM
STAT- MEDLINE
DCOM- 20050106
LR  - 20220316
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1705
IP  - 2
DP  - 2004 Dec 17
TI  - The role of gelatinases in colorectal cancer progression and metastasis.
PG  - 69-89
AB  - Various proteases are involved in cancer progression and metastasis. In 
      particular, gelatinases, matrix metalloproteinase-2 (MMP-2) and MMP-9, have been 
      implicated to play a role in colon cancer progression and metastasis in animal 
      models and patients. In the present review, the clinical relevance and the 
      prognostic value of messenger ribonucleic acid (mRNA) and protein expression and 
      proenzyme activation of MMP-2 and MMP-9 are evaluated in relation to colorectal 
      cancer. Expression of tissue inhibitors of MMPs (TIMPs) in relation with MMP 
      expression in cancer tissues and the relevance of detection of plasma or serum 
      levels of MMP-2 and/or MMP-9 and TIMPs for prognosis are also discussed. 
      Furthermore, involvement of MMP-2 and MMP-9 in experimental models of colorectal 
      cancer is reviewed. In vitro studies have suggested that gelatinase is expressed 
      in cancer cells but animal models indicated that gelatinase expression in 
      non-cancer cells in tumors contributes to cancer progression. In fact, 
      interactions between cancer cells and host tissues have been shown to modulate 
      gelatinase expression in host cells. Inhibition of gelatinases by synthetic MMP 
      inhibitors has been considered to be an attractive approach to block cancer 
      progression. However, despite promising results in animal models, clinical trials 
      with MMP inhibitors have been disappointing so far. To obtain more insight in the 
      (patho)physiological functions of gelatinases, regulation of MMP-2 and MMP-9 
      expression is discussed. Mitogen activated protein kinase (MAPK) signalling has 
      been shown to be involved in regulation of gelatinase expression in both cancer 
      cells and non-cancer cells. Expression can be triggered by a variety of stimuli 
      including growth factors, cytokines and extracellular matrix (ECM) components. On 
      the other hand, MMP-2 and MMP-9 activity regulates bioavailability and activity 
      of growth factors and cytokines, affects the immune response and is involved in 
      angiogenesis. Because of the multifunctionality of gelatinases, it is 
      unpredictable at what stage of cancer development and in which processes 
      gelatinase activity is involved. Therefore, it is concluded that the use of MMP 
      inhibitors to treat cancer should be considered carefully.
FAU - Mook, Olaf R F
AU  - Mook OR
AD  - Academic Medical Center, University of Amsterdam, Department of Cell Biology and 
      Histology, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
FAU - Frederiks, Wilma M
AU  - Frederiks WM
FAU - Van Noorden, Cornelis J F
AU  - Van Noorden CJ
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Cytokines)
RN  - 0 (Growth Substances)
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.24.- (Gelatinases)
SB  - IM
MH  - Animals
MH  - Colorectal Neoplasms/*enzymology/pathology
MH  - Cytokines/pharmacology
MH  - Disease Progression
MH  - Extracellular Matrix/metabolism
MH  - Gelatinases/antagonists & inhibitors/blood/genetics/*physiology
MH  - Gene Expression Regulation, Neoplastic
MH  - Growth Substances/pharmacology
MH  - Humans
MH  - Neoplasm Metastasis
MH  - Neovascularization, Pathologic
MH  - Prognosis
MH  - RNA, Messenger/metabolism
RF  - 197
EDAT- 2004/12/14 09:00
MHDA- 2005/01/07 09:00
CRDT- 2004/12/14 09:00
PHST- 2004/12/14 09:00 [pubmed]
PHST- 2005/01/07 09:00 [medline]
PHST- 2004/12/14 09:00 [entrez]
AID - S0304-419X(04)00062-9 [pii]
AID - 10.1016/j.bbcan.2004.09.006 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2004 Dec 17;1705(2):69-89. doi: 
      10.1016/j.bbcan.2004.09.006.