Corrélation entre la protéase de la matrice extracellulaire MMP2 et le pronostic du cancer de la prostate : étude des mécanismes sous-jacents
|Abstract:||Introduction: The matrix metalloproteinase 2 (MMP2) is associated with poor prognosis in many neoplasms. MMP14 activates MMP2 using pro-MMP2 specific inhibitor TIMP2 as a receptor. Activated MMP2 degrades extracellular matrix components such as collagen and gelatin, and activates other MMPs including MMP9 (gelatinase B). We therefore tested the influence of MMP9, MMP14 and TIMP2 expression on prostate cancer (Pca) disease-free survival and the association between MMP2, MMP9, MMP14 and TIMP2. Stromal MMP14 involvement in tumor growth was also tested. Material and methods: By immunohistochemistry, we analyzed 200 T3NxM0 Pca cases. We evaluated marker expression separately in cancer, stromal and benign epithelial (BE) cells according to a percentage scale (0, < 10, 10-50 and ≥ 50%) and to low (< 10%) or high (≥ 10%) expression of the markers. MCF7 cells were injected subcutaneously to nu/nu mice with MMP14 -/- fibroblasts and their growth was compared to MCF7 + MMP14 +/+ fibroblasts tumors. Results: Median follow-up was 4.61 years. MMP9 overexpression in cancer cells was associated with high Gleason score (8-10) (p = 0.0009). Low initial PSA serum levels (≤ 20ng/ml) were indirectly associated with MMP14 overexpression in BE cells (p = 0.0027) and with MMP9 overexpression in stromal (p = 0.0050) and BE cells (p = 0.0056). There was a decreased risk of Pca recurrence with high (≥ 10%) TIMP2 expression in stromal cells (hazard ratio (HR) = 0.573, p = 0.0233) and an increased risk of Pca recurrence with MMP2 expression by > 50% of BE cells (HR = 3.006, p = 0.0387). Increased risk of Pca recurrence was also observed with high MMP2 expression (HR = 1.549, p = 0.0027, trend test) and with the following combinations: low TIMP2 in stromal cells and high MMP2 in BE cells (HR = 4.121, p < 0.0001); high MMP2 in stromal cells and low TIMP2 in cancer cells (HR = 2.742, p = 0.0171). MCF7 studies suggest MMP14 stromal involvement in Pca implantation. Conclusions: MMP9 and MMP14 are involved mostly in Pca implantation. MMP2 and TIMP2 might be used as predictors of disease-free survival in T3NxM0 Pca.|
|Document Type:||Mémoire de maîtrise|
|Open Access Date:||11 April 2018|
|Collection:||Thèses et mémoires|
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