Expression of matrix metalloproteinase-10 in human bladder transitional cell carcinoma.
OBJECTIVE
To analyze matrix metalloproteinase-10 (MMP-10) expression in transitional cell carcinoma (TCC) of the bladder, evaluate the correlations between MMP-10 protein expression and clinicopathologic parameters, and address the viability of MMP-10 as a therapeutic target for TCC. MMP-mediated degradation of the extracellular matrix is an important factor in the pathogenesis of tumorigenesis and metastasis.


METHODS
Using immunohistochemistry, the expression of MMP-10 was assessed using both tissue microarrays and whole sections of archival tissue specimens representative of all grades and stages of human bladder TCC (n = 60). MMP-10 expression was also assessed in histologically normal human bladder tissue (n = 10). The immunostaining results for MMP-10 expression were examined for correlations with tumor grade and stage.


RESULTS
Unlike most MMPs, MMP-10 was localized primarily in the tumor mass as opposed to the tumor stroma and was detectable in all grades and stages of TCC. Significantly greater levels of MMP-10 protein were observed in superficial (pTa, pT1; n = 38) tumors than in normal bladder tissue (P = 0.01). In contrast to the proposed role of MMPs in tumor invasion, no significant difference was observed between muscle-invasive tumors (pT2 or worse; n = 22) and histologically normal bladder tissue (P = 0.50). MMP-10 expression showed no significant correlation with tumor grade.


CONCLUSIONS
The data from our study showed that, unlike most MMPs, MMP-10 was not associated with tumor aggression or invasion. Our results suggest that MMP-10 protein levels are significantly greater in the earlier stages of TCC development.
Seargent
Jill M
JM
Cancer Research UK Laboratories, Tom Connors Cancer Research Centre, University of Bradford, Bradford, United Kingdom.
Loadman
Paul M
PM
Martin
Sandie W
SW
Naylor
Brian
B
Bibby
Michael C
MC
Gill
Jason H
JH
D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases / Q000032:analysis / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000378:metabolism*
D008666:Metalloendopeptidases; D053506:Matrix Metalloproteinase 10