OBJECTIVES: 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.
OBJECTIVES: 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.
Authors: Brett D McKinnon; Samuel W Lukowski; Sally Mortlock; Joanna Crawford; Sharat Atluri; Sugarniya Subramaniam; Rebecca L Johnston; Konstantinos Nirgianakis; Keisuke Tanaka; Akwasi Amoako; Michael D Mueller; Grant W Montgomery Journal: Commun Biol Date: 2022-06-20