PMID- 18423620
OWN - NLM
STAT- MEDLINE
DCOM- 20080915
LR  - 20151119
IS  - 0014-4835 (Print)
IS  - 0014-4835 (Linking)
VI  - 86
IP  - 6
DP  - 2008 Jun
TI  - Expression and distribution of MMPs and TIMPs in human uveal melanoma.
PG  - 936-41
LID - 10.1016/j.exer.2008.03.010 [doi]
AB  - Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are 
      involved in tumour invasion, metastasis and angiogenesis, and have been 
      implicated as progression markers in uveal melanoma, although their topographical 
      expression has not been fully described. In this study we compared the 
      distribution and specificity of several classes of MMPs (MMP-1, -2, -9, -19, and 
      MT1-MMP) and physiological MMP inhibitors (TIMP-2 and -3) in different regions of 
      the tumour microenvironment and adjacent choroid in a series of primary uveal 
      melanomas. Paraffin sections of untreated uveal melanomas (n=18, 3/18 spindle; 
      11/18 mixed, and 4/18 epithelioid) were examined for MMP-1 (collagenase 1), MMP-2 
      and MMP-9 (gelatinases A and B), MT1-MMP (membrane-type 1-MMP), MMP-19, TIMP-2 
      and TIMP-3 (tissue inhibitors of MMPs), using indirect peroxidase 
      immunohistochemistry. The distribution and intensity of immunolabelling was 
      graded semi-quantitatively (0-3) by 2 independent observers. Non-parametric 
      analyses were used to test for associations between tumour cell type, and the 
      average grade of MMP or TIMP expression. Immunostaining for MMP-1, -9, -19 and 
      MT1-MMP was > or =Grade 2 in more than 70% of specimens, and a heterogeneous 
      pattern of MMP-1, -9, MT1-MMP and TIMP-3 expression was observed. At the 
      tumour-scleral interface (TSI), melanoma cells had a flattened morphology and a 
      much reduced MMP and TIMP expression, with a high expression in tumour areas 
      adjacent to the TSI. Tumour vasculature and stromal cells strongly expressed 
      MMP-2. We also observed heterogeneous immunostaining of the vasculature by MMP-1, 
      -9, MT1-MMP and TIMP-2 antibodies, and of the extravascular matrix by MMP-9 
      antibody. The distinct immunostaining patterns observed for MMPs and TIMPs within 
      uveal melanoma are consistent with their involvement in tumour growth and 
      angiogenesis. In particular, the heterogeneous expression within regions of the 
      tumours, and the localized expression in vasculature and stromal cells emphasises 
      the importance of the tumour microenvironment in the pathogenesis of uveal 
      melanoma (and other tumours).
FAU - Lai, K
AU  - Lai K
AD  - Save Sight Institute & Discipline of Ophthalmology, University of Sydney, Sydney, 
      NSW, Australia.
FAU - Conway, R M
AU  - Conway RM
FAU - Crouch, R
AU  - Crouch R
FAU - Jager, M J
AU  - Jager MJ
FAU - Madigan, M C
AU  - Madigan MC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080316
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Matrix Metalloproteinases/*metabolism
MH  - Melanoma/blood supply/*metabolism/pathology
MH  - Middle Aged
MH  - Neoplasm Proteins/metabolism
MH  - Neovascularization, Pathologic/metabolism
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
MH  - Uveal Neoplasms/blood supply/*metabolism/pathology
EDAT- 2008/04/22 09:00
MHDA- 2008/09/16 09:00
CRDT- 2008/04/22 09:00
PHST- 2007/09/24 00:00 [received]
PHST- 2008/02/29 00:00 [revised]
PHST- 2008/03/06 00:00 [accepted]
PHST- 2008/04/22 09:00 [pubmed]
PHST- 2008/09/16 09:00 [medline]
PHST- 2008/04/22 09:00 [entrez]
AID - S0014-4835(08)00097-3 [pii]
AID - 10.1016/j.exer.2008.03.010 [doi]
PST - ppublish
SO  - Exp Eye Res. 2008 Jun;86(6):936-41. doi: 10.1016/j.exer.2008.03.010. Epub 2008 
      Mar 16.