Expression and Clinical Significance of Metalloproteases and Their Inhibitors by Endothelial Cells From Invasive Breast Carcinomas

Abstract

Background: Given that tumor blood vessels are important in tumor progression and metastasis, tumor endothelial cells (ECs) are the main targets of antiangiogenic therapy. The aim of the present work was to evaluate the phenotype of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) from ECs at the tumor center and its relationship to MMP/TIMP global expression and its relationship to the occurrence of distant metastasis.

Patients and methods: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs (MMP-2, -7, -9, -11, -13, and -14) and TIMPs (TIMP-1, -2, and -3) at the tumor center in 104 patients with primary ductal invasive breast tumors.

Results: MMP-11 expression by ECs was related to shorter relapse-free survival, whereas TIMP-3 expression was related to low occurrence of distant metastasis. In addition, MMP-11 and TIMP-2 expression by ECs was associated with shorter overall survival, whereas TIMP-3 expression by ECs was associated with longer overall survival. Our findings indicate significant relationships between the expression of MMPs/TIMPs by ECs and the global expression of these factors at the tumor scene.

Conclusion: High MMP/TIMP expression by ECs from breast carcinomas, which may be consequence of the cross-talk between tumor cells and their surrounding microenvironment.

Keywords: Breast cancer; MMP; Prognosis; TIMP; Tumor stroma.