MMP11 expression in intratumoral inflammatory cells in breast cancer

Abstract

Aims It is known that matrix metalloproteinase (MMP)‐11 has a role in tumour development and progression, and also that immune cells can influence cancer cells to increase their proliferative and invasive properties. The aim of the present study was to propose the evaluation of MMP11 expression by intratumoral mononuclear inflammatory cells (MICs) as a useful biological marker for breast cancer prognosis. Methods and results This study comprised 246 women with invasive breast carcinoma, and a long follow‐up period. Patients were stratified with regard to nodal status and to the development of metastatic disease. The median follow‐up period in patients without metastasis was 146 months and in patients with metastatic disease 31 months. MMP11 was determined by immunohistochemistry. For relapse‐free survival (RFS) and overall survival (OS) analysis we used the Cox’s univariate method. Cox’s regression model was used to examine the interactions between different prognostic factors in a multivariate analysis. Conclusions Our results showed that MMP11 expression by stromal cells was significantly associated with prognosis. MMP11 expression by cancer‐associated fibroblasts (CAFs) was associated with both shortened RFS and OS, but MMP11 expression by MICs showed a stronger association with both shortened RFS and OS, therefore being the most potent and independent factor to predict RFS and OS.

MMP1 and MMP11 Expression in Peripheral Blood Mononuclear Cells upon Their Interaction with Breast Cancer Cells and Fibroblasts

“…The fact that IL10 expression was strongly induced in NF and CAF co-cultured with BC-PBMC indicates that BC-PBMC could be instrumental in the induction of immune tolerance against breast cancer cells and thus a suppression of an anti-tumoral immune response by upregulating IL10. In addition, these results support the implication of MMP11 expression by inflammatory cells, but not by fibroblasts, in the context of dynamic tumor-stroma interactions, and its relationship with clinical outcome [15]. In addition, these inflammatory factors, besides their central role in the inflammation process, have been related to distant metastasis promotion [12] due to their role in tumor progression through several pathways, including the generation of free radicals that can induce DNA damage and mutations that can lead to tumor initiation, stimulating cell proliferation and reducing apoptosis, promoting EMT, and angiogenesis [41][42][43].…”

“…In previous studies, we have proved that tumor-infiltrating immune cells expressing high levels of MMPs had a higher rate of distant metastasis development compared with tumors with low expression profile of MMPs in immune cells [6][7][8][9][10][11]. In particular, the expression of MMP11 in tumor-infiltrating immune cells was highly associated with both distant metastasis development and high inflammatory profile in breast cancer [10][11][12][13][14][15]. In addition, we have shown that CAF from MMP11 positive tumor-infiltrating immune cells tumors may overexpress tumor progression factors and may show higher breast cancer cell invasion and angiogenesis [16,17].…”

MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma

“…MMP11 is a protein-coding gene, and MMP25 is an important paralog of this gene. MMP11, a zincdependent endopeptidase and the main protease involved in ECM degradation, plays an important role in various biological processes, such as breast cancer [13], prostate cancer [9], gastric cancer [41], and lung cancer [42], where the high expression of MMP11 is associated with metastasis and a poor clinical outcome. Furthermore, several studies have shown that MMP11…”

“…In recent years, studies have shown that MMPs expression is associated with the occurrence and development of a variety of tumors. These molecules are important in the growth and invasion of malignant tumors, and their expression has an important impact on the prognosis of patients [13][14][15][16]. However, there are few reports on the MMPs gene family role in the prognosis of UVM.…”

MMP11 promotes the proliferation and progression of breast cancer through stabilizing Smad2 protein

“…A previous study revealed that high expression of MMP11 in BC was associated with a poor prognosis in patients (8). MMP11 was revealed to promote tumour malignancy by inhibiting apoptosis and by promoting migration and invasion, but the underlying mechanism remains unclear (9,10).…”