PMID- 14678978
OWN - NLM
STAT- MEDLINE
DCOM- 20040227
LR  - 20061115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 23
DP  - 2003 Dec 1
TI  - Expression of matrix metalloproteinases in the microenvironment of spontaneous 
      and experimental melanoma metastases reflects the requirements for tumor 
      formation.
PG  - 8221-5
AB  - Expression of matrix metalloproteinases (MMPs) and their activation in tumor 
      cells, as well as tumor surrounding stromal cells have been implicated in tumor 
      cell invasion and metastasis. By means of a syngeneic tumor model for either 
      experimental or spontaneous metastases, the differential expression of MMPs and 
      tissue inhibitors of MMPs (TIMPs) in relation to the microenvironment and the way 
      of metastasis induction was characterized. In vitro characterization revealed 
      that increased levels of secreted MMP-2, MMP-9, and TIMP-1 were only detectable 
      in the most aggressive cell line, B16G3.12BM2. Remarkably, active MMP-2 was 
      restricted to this cell line, whereas TIMP-2 and membrane type (MT) 1-MMP 
      expression was comparable in all three of the spontaneously metastasizing 
      melanoma cell lines investigated. In vivo analysis demonstrated that MMP-2, 
      MMP-9, and MT1-MMP were predominantly expressed at the tumor-stroma border of 
      s.c. tumors. Furthermore, functional active MMP-2 was restricted to this invasive 
      front. In spontaneous lymph node or lung metastases, however, MMP-9 was expressed 
      both in the center and the periphery of tumors; these areas were largely negative 
      for MMP-2 and MT1-MMP. Notably, tumor cells of experimental lung metastases did 
      not express MMP-9 at all. These results indicate that expression of MMPs in 
      melanoma metastases is not only influenced by their localization but also the 
      nature of tumor induction, suggesting that individual MMPs serve specific roles 
      during the different stages of metastasis formation.
FAU - Hofmann, Uta B
AU  - Hofmann UB
AD  - Department of Dermatology, Julius Maximilian's University, Wurzburg, Germany. 
      hofmann.ul@klinik.uni-wuerzburg.de
FAU - Eggert, Andreas A O
AU  - Eggert AA
FAU - Blass, Katharina
AU  - Blass K
FAU - Brocker, Eva-B
AU  - Brocker EB
FAU - Becker, Jurgen C
AU  - Becker JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Mmp14 protein, mouse)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.80 (Matrix Metalloproteinase 14)
SB  - IM
MH  - Animals
MH  - Female
MH  - Lung Neoplasms/enzymology/secondary
MH  - Lymphatic Metastasis
MH  - Matrix Metalloproteinase 14
MH  - Matrix Metalloproteinase 2/biosynthesis
MH  - Matrix Metalloproteinase 9/biosynthesis
MH  - Matrix Metalloproteinases/*biosynthesis
MH  - Matrix Metalloproteinases, Membrane-Associated
MH  - Melanoma, Experimental/*enzymology/pathology/*secondary
MH  - Metalloendopeptidases/biosynthesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Tissue Inhibitor of Metalloproteinase-1/biosynthesis
MH  - Tissue Inhibitor of Metalloproteinase-2/biosynthesis
EDAT- 2003/12/18 05:00
MHDA- 2004/02/28 05:00
CRDT- 2003/12/18 05:00
PHST- 2003/12/18 05:00 [pubmed]
PHST- 2004/02/28 05:00 [medline]
PHST- 2003/12/18 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Dec 1;63(23):8221-5.