Comparative analysis and clinical value of the expression of metalloproteases and their inhibitors by intratumour stromal mononuclear inflammatory cells and those at the invasive front of breast carcinomas

Abstract

Our data led us to consider the need of further studies in order to identify subsets of MICs and other protein elements of the microenvironment as attractive targets for new therapeutic strategies against cancer.

Prognostic Value of Matrix Metalloproteinase 9 Expression in Breast Cancer Patients: A Meta-analysis

“…There was no significant heterogeneity among the studies that assessed the prognostic value of MMP-9 expression by OS (P=0.360, I 2 =8.8%), while heterogeneity was observed by RFS (P=0.002, I 2 =67.0%). Galbraith plot discovered that two studies (Vizoso et al, 2007;Gonzalez et al, 2010) may be the principal contributor to the heterogeneity .…”

“…MMP-9 mRNA expression was evaluated in another study (Sieuwerts et al, 2005). Furthermore, two studies (Pellikainen 2004;Gonzalez et al, 2010) provided information about MMP-9 expression in tumor cells and stromal tissues respectively without general result, which we treated independently. Eventually, 15 studies met the inclusion criteria were included (Scorilas et al, 2001;Fan et al, 2003;Li et al, 2004;Pellikainen et al, 2004;Rahko et al, 2004;Li et al, 2006;Mylona et al, 2007;Vizoso et al, 2007;Feng et al, 2008;Wu et al, 2008;Zhao et al, 2008;Tian et al, 2009;Gonzalez et al, 2010;Sullu et al, 2011;Oscar et al, 2012).…”

Clinical Relevance of Matrix Metalloproteases and their Inhibitors in Breast Cancer

“…In addition, these two differential MICs phenotypes with distinct prognosis were also found in breast carcinomas with luminal A or in basal-like phenotype [133], which suggests the importance of the expression of MMPs/TIMPs by the stromal cells as prognostic factors independently of the signature of cancer cells. These two tumor groups were present at the invasive front of tumors, but it was also possible to identify a third group of tumors who's MICs showed an intermediate MMP/TIMP expression profile [134]. These findings suggest that tumor-infiltrating leukocytes from peripheral blood undergo a phenotypic modification to infiltrate from the invasive front into the tumor center.…”

“…These associations are relevant because these highly expressed genes have been associated with several biological mechanisms related to tumor progression [151][152][153][154][155][156][157]. It is also relevant the novel finding of the association between the expression of MMP-11 or TIMP-2 by the MICs at the tumor center and a high CD68/(CD3+CD20) ratio (macrophages (CD68 [158], since both proteins are the two principal factors defining the prometastatic phenotype of MICs in our previous studies [34,132,134,144]. In addition, if there is a high CD68/(CD3+CD20) ratio at the invasive front, most of MICs with a positive MMP-11 or TIMP-2 phenotype at the tumor center are macrophages, suggesting all these findings that a high CD68/(CD3+CD20) ratio at the invasive front contributes to polarize macrophages to achieve a high metastatic phenotype at the tumor center.…”

“…Role in distant metastasis development As described more above, patients with high MMP/TIMP expression pattern in the corresponding MICs populations at the tumor center, as well as at the invasive front, had the highest probability to develop distant metastases [134]. Also, we demonstrated that MMP-11 was the most frequently expressed protein in these prometastatic-related MICs (85.7% vs. 4.6% in the low MMPs/TIMPs profile group), and therefore its expression was considered as a useful biological marker in these MICs population [132].…”