PMID- 11716069
OWN - NLM
STAT- MEDLINE
DCOM- 20020506
LR  - 20220408
IS  - 0167-594X (Print)
IS  - 0167-594X (Linking)
VI  - 53
IP  - 2
DP  - 2001 Jun
TI  - Glioma cell invasion: regulation of metalloproteinase activity by TGF-beta.
PG  - 177-85
AB  - Matrix metalloproteinases (MMPs) are a family of extracellular endopeptidases 
      that selectively degrade components of the extracellular matrix. MMPs are 
      implicated in tumor cell invasion because they mediate the breakdown of the basal 
      membrane. In addition, they seem to be important for the creation and maintenance 
      of a microenvironment that facilitates tumor cell survival. Among the essential 
      characteristics of human malignant gliomas are infiltrative growth, angiogenesis 
      and suppression of antitumor immune surveillance. Transforming growth factor-beta 
      (TGF-beta) is intimately involved in the regulation of these processes. We have 
      previously demonstrated that TGF-beta promotes the migration of LN- 18 and LN-229 
      glioma cells via a process that may involve the upregulation of alphaVbeta3 
      integrin expression. Furthermore, we have defined a novel pathway for hepatocyte 
      growth factor (HGF)-induced glioma cell migration and invasion which requires the 
      induction of TGF-beta2 expression. Here, we demonstrate that TGF-beta2 induces 
      MMP-2 expression and suppresses tissue inhibitor of metalloproteinases (TIMP)-2 
      expression and that concentration-dependently promotes the invasion of U87MG and 
      LN-229 glioma cells in a matrigel invasion assay. Similarly, ectopic expression 
      of the anti-apoptotic BCL-x, protein leads to enhanced matrigel invasion by LN-18 
      and LN-229 glioma cells. We outline the possible interrelations of TGF-beta, 
      proteins of the BCL-2 family, integrins and metalloprotease activity. By virtue 
      of its promotion of glioma invasion and its growth regulatory and 
      immunomodulatory properties. TGF-beta continues to be one of the most promising 
      targets for the experimental therapy of human malignant glioma.
FAU - Wick, W
AU  - Wick W
AD  - Department of Neurology, University of Tubingen, Germany. 
      wolfgang.wick@uni-tuebingen.de
FAU - Platten, M
AU  - Platten M
FAU - Weller, M
AU  - Weller M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (Bcl2l1 protein, mouse)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteoglycans)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Vitronectin)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (TGFB2 protein, human)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Transforming Growth Factor beta2)
RN  - 0 (bcl-X Protein)
RN  - 0 (ezrin)
RN  - 119978-18-6 (matrigel)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Brain Neoplasms/enzymology/*pathology
MH  - Cell Movement
MH  - Collagen
MH  - Cytoskeletal Proteins
MH  - Drug Combinations
MH  - Enzyme Induction/drug effects
MH  - Extracellular Matrix/metabolism
MH  - Glioma/enzymology/*pathology
MH  - Humans
MH  - Laminin
MH  - Matrix Metalloproteinase 2/*biosynthesis/genetics
MH  - Mice
MH  - Neoplasm Invasiveness/*physiopathology
MH  - Neoplasm Proteins/*biosynthesis/genetics
MH  - Phosphoproteins/genetics/physiology
MH  - Proteoglycans
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis/genetics
MH  - Receptors, Vitronectin/biosynthesis/genetics
MH  - Recombinant Proteins/pharmacology
MH  - Tissue Inhibitor of Metalloproteinase-2/biosynthesis/genetics
MH  - Transfection
MH  - Transforming Growth Factor beta/*pharmacology/physiology
MH  - Transforming Growth Factor beta1
MH  - Transforming Growth Factor beta2
MH  - Tumor Cells, Cultured/drug effects/enzymology/pathology
MH  - bcl-X Protein
RF  - 60
EDAT- 2001/11/22 10:00
MHDA- 2002/05/07 10:01
CRDT- 2001/11/22 10:00
PHST- 2001/11/22 10:00 [pubmed]
PHST- 2002/05/07 10:01 [medline]
PHST- 2001/11/22 10:00 [entrez]
AID - 10.1023/a:1012209518843 [doi]
PST - ppublish
SO  - J Neurooncol. 2001 Jun;53(2):177-85. doi: 10.1023/a:1012209518843.