Expression and clinical significance of metalloproteases and their inhibitors by endothelial cells from invasive breast carcinomas

Abstract

Aims: Given that tumor blood vessels are important in tumor progression and metastasis, tumor endothelial cells are the main targets of anti-angiogenic therapy. The aim of the present work was to evaluate the phenotype of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) from endothelial cells (ECs) at the tumor center and its relationship with MMPs/TIMPs global expression, as its relationship with the occurrence of distant metastasis. Methods: An inmunohistochemical study was performed using tissue arrays and specific antibodies against MMPs (2, 7, 9, 11, 13 and 14) and TIMPs (1, 2 and 3), at tumor center in 104 patients with primary ductal invasive breast tumors. Results: Our results demonstrated that MMP-11 expression by ECs was related with a shortened relapse-free survival, whereas TIMP-3 expression was related with low occurrence of distant metastasis. In addition, MMP-11 and TIMP-2 expression by ECs was associated with a shortened 3 overall survival, whereas TIMP-3 expression by ECs was associated with a higher overall survival. However, our findings indicate significant relationships between the expression of MMPs/TIMPs by ECs and the global expression of these factors at the tumor scene. Conclusions: The present work shows a high MMPs/TIMPs expression by ECs from breast carcinomas, which may be consequence of the crosstalk between tumor cells and their surrounding microenvironment.